Immunology Letters[JOURNAL]
Sun
200 papers
The cancer-immunity cycle in motion: The effects of exercise on antitumor immunity.
Leuchte K, Trommer M, Holmen Olofsson G … +1 more , Thor Straten P
Immunol Lett · 2026 Feb · PMID 41061895 · Publisher ↗
Physical activity has recently emerged as a promising modulator of antitumor immunity, but the underlying mechanisms are incompletely understood. Here, we review human studies assessing the effects of exercise on the sin...
Physical activity has recently emerged as a promising modulator of antitumor immunity, but the underlying mechanisms are incompletely understood. Here, we review human studies assessing the effects of exercise on the single steps of the cancer-immunity cycle. Interventions were mostly based on acute or continuous high- and moderate-intensity endurance exercise, followed by analyses of immune cell function and serum markers. There is evidence that exercise enhances tumor cell susceptibility to apoptosis and promotes dendritic cell maturation via damage-associated molecular patterns. Catecholamine-mediated NK and CD8T cell mobilization facilitates trafficking to tumors, further supported by vascular and metabolic changes to the tumor microenvironment. Overall, there is evidence from human studies that exercise improves immune cell effector function at different steps of the cancer-immunity cycle, thereby potentiating antitumor responses. These findings support the integration of structured exercise therapy into cancer care, possibly in combination with immunotherapeutic strategies. Further mechanistic and clinical research is warranted to optimize exercise-based interventions.
Profiling of circulating T follicular helper and T peripheral helper cell subsets in patients with primary biliary cholangitis.
Ma H, Liu Y, Zhu Y … +9 more , Xu G, Xiang X, Xue S, Zhang Z, Cheng C, Lu F, Wang B, Zhang Y, Jiang T
Immunol Lett · 2026 Feb · PMID 41046875 · Publisher ↗
Primary biliary cholangitis (PBC) is a common chronic cholestatic autoimmune liver disease that may progress to liver fibrosis or cirrhosis if not accurately diagnosed and promptly treated. T follicular helper (Tfh) cell...
Primary biliary cholangitis (PBC) is a common chronic cholestatic autoimmune liver disease that may progress to liver fibrosis or cirrhosis if not accurately diagnosed and promptly treated. T follicular helper (Tfh) cells and T peripheral helper (Tph) cells, as subsets of T cells that assist B cells in producing antibodies, are closely related to the pathogenesis of autoimmune diseases. This research aims to explore the potential of Tfh and Tph cells as biomarkers for PBC disease progression. We recruited 30 PBC patients, 25 post-hepatitis B cirrhosis (PHBC) patients, and 30 healthy subjects. Both Tfh and Tph cells were significantly enriched in the peripheral blood of PBC patients, and their frequencies were correlated with autoantibody production. Area under the ROC curve (AUC) analysis demonstrated that Tfh and Tph cell frequencies exhibited convergent diagnostic performance with anti-mitochondrial antibody (AMA) in discriminating PBC patients from healthy controls. Furthermore, the frequencies of these cells were positively correlated with liver enzyme levels (ALT, AST, and GGT), suggesting that they may indicate liver and bile duct damage in PBC patients. The frequency of Tfh cells was negatively correlated with total protein (TP) and albumin (ALB) levels, indicating that the increase of Tfh cells was related to the impairment of hepatocyte function. Additionally, the frequencies of Tfh and Tph cells were positively correlated with IgM levels, showing that these cells seem to be involved in the production of immunoglobulins. Together, Tfh and Tph cells can serve as biomarkers for both diagnosing PBC and correlating with disease severity.
CD4 and CD8 T-cell lymphocytes from penile squamous cell carcinoma tumors are more differentiated with higher PD-1 expression compared to lymphocytes in peripheral circulation.
Mumba C, Mwale NK, Mapulanga V … +1 more , Ngalamika O
Immunol Lett · 2026 Feb · PMID 41045992 · Full text
BACKGROUND: Penile squamous cell carcinoma (PSCC) is the commonest malignancy of the penis, with a higher incidence and poor treatment outcomes in developing countries. T-cell phenotypes have been shown to identify patie...
BACKGROUND: Penile squamous cell carcinoma (PSCC) is the commonest malignancy of the penis, with a higher incidence and poor treatment outcomes in developing countries. T-cell phenotypes have been shown to identify patients who may respond favorably to immune therapy, and also associate with treatment outcomes. This study aimed to determine and compare the tumor and peripheral blood T-cell phenotypes of individuals with PSCC, and whether factors such as smoking and presence of HPV associate with these T-cell phenotypes. METHODS: We conducted a prospective cross-sectional study at the University Teaching Hospital, Lusaka, Zambia. Participants with a histologically-confirmed PSCC were recruited into the study. Socio-demographic information was obtained, and whole blood was collected and subjected to peripheral blood mononuclear cells (PBMCs) isolation. Fresh penile tumors were mechanically and enzymatically digested. CD4 and CD8 cells were sorted from PBMCs and tumor, stained using antibodies against CD3, CD45RO, CCR7, PD-1, CD103 and CD69, and subjected to flow cytometry. Parts of the tumor were subjected to HPV detection, and histological grading and staging. RESULTS: Twenty-four participants were recruited into the study. The median age was 55.5 years, 45.8 % were smokers, 87.5 % were HIV positive, 62.5 % had high-risk HPV detected in the tumors, and 25 % had advanced-stage disease. There was a significantly higher proportion of naïve cells among CD4 T-cells from PBMCs than tumor (40.2 % vs 3.8 %; p = 0.01). CD4 T cells from the tumor demonstrated a significantly higher proportion of cells expressing CD69 (3.2 % vs 95.9 %; p = 0.0001), CD103 (0.7 % vs 7.3 %; p = 0.0001), and PD-1 (35.5 % vs 92 %; p = 0.0001) than the ones from PBMCs. Tumoral CD8 T-cells had a significantly lower proportion of terminally-differentiated effector cells but higher proportion of central memory cells compared to PBMCs, (7.9 % vs 15.1 %, p = 0.04) and (55 % vs 14.4 %; p = 0.01) respectively. Tumoral CD8 T-cells also had a significantly higher proportion of cells expressing CD69 (96.7 % vs 8.5 %; p = 0.0001), CD103 (22.2 % vs 1.2 %; p = 0.0001), and PD-1 (79.3 % vs 18.8 %; p = 0.0001) when compared to the PBMCs. Early-stage disease was associated with a significantly higher proportion of central memory CD4 T-cells among the PBMCs when compared with advanced stage disease (46.7 % vs 30 %; p = 0.01), while smoking was associated with a significantly higher proportion of tumoral CD8 T-cells expressing the homing marker CD103 (28.2 % vs 17.8 %; p = 0.01). CONCLUSION: PSCC tumors demonstrate a higher proportion of primed T-cells with a memory phenotype compared to T-cells in the circulation. T-cells from PSCC tumors also have a higher proportion of cells expressing the immune checkpoint PD-1 and homing markers than those from the circulation.
Immunological features driving distinct repigmentation patterns in patients with stable vitiligo submitted to the autologous keratinocyte/melanocyte transplantation.
Frias BED, Prado RO, Ramos MG … +14 more , Oliveira NWC, Araújo FF, Santos LMD, Ramos CG, Kallás CB, Sousa MSLA, Costa-Rocha IA, Brito-de-Sousa JP, Caligiorne RB, Pascoal-Xavier MA, Peruhype-Magalhães V, Ramos DG, Teixeira-Carvalho A, Martins-Filho OA
Immunol Lett · 2026 Feb · PMID 41045991 · Publisher ↗
This study aimed to characterize biomarkers of therapeutic response in patients with stable vitiligo undergoing the autologous non-cultured keratinocyte/melanocyte transplantation. The approaches performed were systemic...
This study aimed to characterize biomarkers of therapeutic response in patients with stable vitiligo undergoing the autologous non-cultured keratinocyte/melanocyte transplantation. The approaches performed were systemic analysis evaluated during pre-transplantation/(D0), seven/(D7), and 28 or more/(D28-45) days after the procedure and compartmentalized analysis in epidermal cell suspension (explant). Increased number of pro-inflammatory monocytes and NK-cells was found during the transplantation follow-up in vitiligo patients compared to the control. There were higher numbers of CD8T-cells and CD4HLA-DRT-cells circulating at D28-45 compared to D0, and increased number of CD8HLA-DRT-cells at D28-45 compared to D7. Decreased levels of the most pro-inflammatory chemokines/cytokines during post-transplantation kinetics timeline were observed. Integrative analysis demonstrated that patients with unsatisfactory repigmentation presented higher numbers of connections between the blood/skin components at D0. The data suggest differentiated profiles in the dynamics of the hematological/immunological biomarkers, according to the kinetics timeline and the clinical outcome of repigmentation in vitiligo patients.
Taurohyodeoxycholic acid ameliorates inflammatory response in a murine model of ovalbumin (OVA)-induced allergic asthma.
You Y, Li J, Wang J … +12 more , Luo X, Liu J, Wang X, Yi S, He R, Shi Y, Xu J, Hou M, Cao Y, Li Y, Dong J, He J
Immunol Lett · 2026 Feb · PMID 41016713 · Publisher ↗
Taurohyodeoxycholic acid (THDCA), a naturally occurring conjugated bile acid compound formed by the condensation of taurine and deoxycholic acid, possesses various biological activities. Present study attempted to assess...
Taurohyodeoxycholic acid (THDCA), a naturally occurring conjugated bile acid compound formed by the condensation of taurine and deoxycholic acid, possesses various biological activities. Present study attempted to assess whether THDCA can alleviate airway inflammation in allergic asthma through regulating the immune balance among CD4T cell subgroups. Mice were exposed with ovalbumin (OVA) to build allergic asthma model and THDCA was administrated orally. Pulmonary histopathology analysis was evaluated by H&E and PAS staining. The typical cytokines and transcription factors of CD4T cell subgroups were determined, and the proportion of CD4T cell subgroups were analyzed. The oral administration of THDCA attenuated OVA-induced asthma by decreasing inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), reducing tIgE and OVA-sIgE concentration in the serum, and improving histopathological changes in the lung tissue. In addition, THDCA reduced the secretion of IL-4, IL-5, IL-13, IL-6, TNF-α, IL-17A, and TGF-β1, but increased the production of IFN-γ, IL-10, and IL-35 in the BALF and lung tissue. Meanwhile, THDCA inhibited GATA3 and RORγt expression, and STAT3 phosphorylation, but improved T-bet and Foxp3 expression in the lung tissue. Besides, THDCA restored the proportion of CD4T cell subgroups in the spleen and peripheral blood. These findings indicated that THDCA may have therapeutic potential for treating allergic asthma by regulating the immune balance of CD4T cell subgroups.
Restoration of Fli1 expression as a potential therapeutic approach in Systemic Sclerosis: Effects on age-associated B cells.
Sachinidis A, Lamprinou M, Dimitroulas T
Immunol Lett · 2026 Feb · PMID 41016712 · Publisher ↗
Fli1 is a transcription factor playing a major role in the regulation of normal hematopoiesis and vasculogenesis. Its deficiency has been associated with the development of fibrosis in various diseases, including systemi...
Fli1 is a transcription factor playing a major role in the regulation of normal hematopoiesis and vasculogenesis. Its deficiency has been associated with the development of fibrosis in various diseases, including systemic sclerosis/scleroderma (SSc), a rare autoimmune rheumatic disease. In addition, in Fli1 B cell conditional knockout mice, a striking increase of age-associated B cells (ABCs) has been observed. These cells constitute a CD11cCD21 B cell population that displays an expansion in autoimmunity and drives disease pathogenesis. The exact role and functions of ABCs, though, are not yet fully understood. Taking into consideration all the above, regarding Fli1 deficiency in SSc pathogenesis and ABC expansion, we propose restoration of this specific transcription factor's expression as a potential therapeutic approach for the aforementioned rheumatic disease. Moreover, we provide some interventions that aim to restore Fli1 expression via modulating the signals of TGF-β pathway, whose activation is considered as crucial for fibrosis development in SSc.
Tryptophan metabolism in health and disease- implications for non-communicable diseases.
Gabela AM, Mthembu N, Hadebe S
Immunol Lett · 2026 Feb · PMID 41015394 · Publisher ↗
Tryptophan, an essential amino acid, is primarily metabolized through four key pathways: the kynurenine pathway, serotonin pathways, indole pathways and interleukin 4-induced gene 1 (IL-4I1) pathways. Dysregulation of tr...
Tryptophan, an essential amino acid, is primarily metabolized through four key pathways: the kynurenine pathway, serotonin pathways, indole pathways and interleukin 4-induced gene 1 (IL-4I1) pathways. Dysregulation of tryptophan metabolism is implicated in various non-communicable diseases including psychiatric disorders, inflammatory and autoimmune diseases, as well as metabolic diseases. The dogma in the field is that tryptophan is metabolized via the kynurenine pathway in the liver mainly by indoleamine 2,3-dioxygenase 1/2 (IDO 1/2) and Tryptophan dioxygenase 2 (TDO2) enzymes. However, there is growing evidence demonstrating that IL-4I1 and tryptophanase are also crucial tryptophan catabolizing enzymes resulting in metabolites that activate aryl hydrocarbon receptor (AhR) and modulate immune responses. Tryptophan metabolism is crucial in cellular, tissue and organismal function and its disruption is linked to conditions such as inflammatory bowel disease (IBD), multiple sclerosis (MS), and psychiatric disorders like depression, anxiety and metabolic diseases such as obesity and Type 2 diabetes. It is unclear though whether only specific tryptophan pathways are associated with disease or there is a level of redundancy. Some key metabolites from tryptophan catabolism can come from multiple pathways, with opposing or converging effects on cellular functions. This review will explore the critical role of tryptophan metabolism in health and diseases, focusing on its implications in non-communicable diseases. Importantly, this review will focus on recent developments in tryptophan metabolism and strengthen the argument for a revised schematic tryptophan catabolic pathway.
Fatty acid binding protein 2 (FATP2/SLC27A2) blockade with Lipofermata elicits dual effects on inflammatory responses in human monocytes and macrophages.
Hahn N, Chornyi S, Heister D … +5 more , de Vries HE, Giera M, Boon MR, Kooij G, Van den Bossche J
Immunol Lett · 2026 Feb · PMID 41015393 · Publisher ↗
Inflammatory responses often involve metabolic rewiring within immune cells to support effector functions. Targeting metabolic pathways in immune cells therefore represents a promising strategy to modulate inflammatory d...
Inflammatory responses often involve metabolic rewiring within immune cells to support effector functions. Targeting metabolic pathways in immune cells therefore represents a promising strategy to modulate inflammatory diseases and improve therapeutic outcomes. Acyl-CoA synthesis by fatty acid transporter 2 (FATP2/SLC27A2) facilitates the transport of long-chain fatty acids into the cell. It represents a key step in fatty acid metabolism and the subsequent production of bioactive lipid mediators (LMs) with immunoregulatory functions. While the FATP2 inhibitor Lipofermata is currently evaluated for lipid-lowering therapies in metabolic diseases, and to revert the suppressive nature of myeloid cells in cancer, its effect on inflammatory responses in human macrophages remains elusive. Here, we show that Lipofermata reduced LPS-induced inflammatory responses in whole blood and human monocytes. This anti-inflammatory effect was paralleled by a decreased biosynthesis of arachidonic acid-derived inflammatory LMs, including prostaglandin E2 (PGE2) and thromboxane 2 (TxB2). These findings suggest an anti-inflammatory effect mediated by Lipofermata-mediated redirection of lipid metabolism in monocytes. Conversely, in mature human monocyte-derived macrophages, Lipofermata treatment enhanced LPS-induced cytokine production and induced cell death, likely through inflammasome activation. Together, these results underscore the cell type-specific effects of FATP2 inhibition and highlight the dual role of Lipofermata in modulating inflammatory immune responses. As such, targeting lipid metabolism with Lipofermata could have therapeutic potential with both anti- and pro-inflammatory applications, depending on the target cell type and context.
Beyond HNA-1: The anti-HNA-3 autoantibody as a protagonist in autoimmune neutropenia.
Cerqueira R, Moritz E, Braga JAP … +3 more , Chiba AK, Pesquero JB, Bordin JO
Immunol Lett · 2026 Feb · PMID 41015392 · Publisher ↗
INTRODUCTION: Autoimmune neutropenia (AIN), a common cause of chronic neutropenia, has been categorized as primary (pAIN) and secondary (sAIN). This study investigates the specificity of anti-HNA autoantibodies in both t...
INTRODUCTION: Autoimmune neutropenia (AIN), a common cause of chronic neutropenia, has been categorized as primary (pAIN) and secondary (sAIN). This study investigates the specificity of anti-HNA autoantibodies in both types. MATERIALS AND METHODS: A prospective cohort study of 85 chronic neutropenia patients included those with detectable anti-HNA autoantibodies. Anti-HNA was assessed using granulocyte agglutination (GAT), granulocyte immunofluorescence (GIFT), and LABScreen Multi Kit (LSM). Molecular analysis was performed to assess HNA expression. RESULTS: Of 85 patients, 7 had pAIN and 8 had sAIN. All pAIN patients exhibited only anti-HNA-1, while anti-HNA-3 was found in 3/8 sAIN patients. All patients with anti-HNA-3 tested positive in LSM; one was positive in both GAT and GIFT. DISCUSSION: While anti-HNA-3 has been described exclusively as an alloantibody, this is the first report of anti-HNA-3 as an autoantibody in AIN. CONCLUSION: Anti-HNA-3 autoantibody is associated only with sAIN, suggesting distinct mechanisms in pAIN and sAIN.
Tissue resident memory B cells mediate protective immunity to respiratory pathogens in the airways.
Akehurst IM, James LK
Immunol Lett · 2026 Feb · PMID 40967276 · Publisher ↗
Respiratory pathogens pose a significant risk to public health and are responsible for burdening health care by causing worldwide morbidity and mortality. The immune environment in the airway is critical for protection f...
Respiratory pathogens pose a significant risk to public health and are responsible for burdening health care by causing worldwide morbidity and mortality. The immune environment in the airway is critical for protection from respiratory pathogens and comprises several specialist subsets of resident lymphocytes and myeloid cells. Tissue resident-memory B cells (B) are a subset of memory B cell which reside in mucosal tissues, including the airways. Although, B have only recently been characterised, they have a crucial role in generating robust and localised immune responses to respiratory infections, particularly secondary responses, by rapidly differentiating into antibody-secreting cells. A greater understanding of their role in protecting the airways from respiratory pathogens will enable the development of immunisation strategies against respiratory disease. This mini-review aims to summarise the current knowledge of B and highlight areas for future research.
Immune checkpoint molecules as predictive markers of COVID-19 severity: A comprehensive univariable and multivariable analysis.
Majchrzak A, Niedźwiedzka-Rystwej P, Bębnowska D … +9 more , Aksak-Wąs B, Karasińska-Cieślak M, Cembrowska-Lech D, Skonieczna-Żydecka K, Mielczak K, Urbańska A, Hrynkiewicz R, Lewandowski F, Parczewski M
Immunol Lett · 2026 Feb · PMID 40962068 · Publisher ↗
Immune dysregulation plays a key role in the deterioration of COVID-19. This study evaluated immune checkpoint molecules (ICMs) as markers of disease severity. Immunophenotyping of 525 hospitalised patients with moderate...
Immune dysregulation plays a key role in the deterioration of COVID-19. This study evaluated immune checkpoint molecules (ICMs) as markers of disease severity. Immunophenotyping of 525 hospitalised patients with moderate (n=464) and severe (n=61) COVID-19 was performed at admission and analysed alongside clinical, laboratory, and imaging data. The strongest correlations with severe outcomes and mortality were found for CD200R+CD3+ T and CD19+ B cells. Significant differences in PD-1+ and PD-L1+ lymphocyte subsets were observed between severity groups. Machine learning (SHAP) confirmed that ICM expression was at least as predictive as conventional risk factors. These findings suggest that markers of immune exhaustion, especially PD-1, PD-L1, and CD200R, may help predict COVID-19 severity. Further research is needed to determine whether targeting immune checkpoints could improve outcomes.
Coordination of cellular responses to SARS-CoV-2 during severe COVID-19 illness.
Samri A, Lhote R, Rousseau A … +10 more , Morin V, Tarantino N, Marot S, Jary A, Sterlin D, Marcelin AG, Amoura Z, Gorochov G, Vieillard V, Guihot A
Immunol Lett · 2026 Feb · PMID 40962067 · Publisher ↗
The early cellular and humoral immune responses to SARS-CoV-2 result in a wide range of COVID-19 disease severity. Here we conducted an observational study of these three arms of the immune responses (T, B and NK) to SAR...
The early cellular and humoral immune responses to SARS-CoV-2 result in a wide range of COVID-19 disease severity. Here we conducted an observational study of these three arms of the immune responses (T, B and NK) to SARS-CoV-2 in 17 patients hospitalized for severe COVID-19 at median of 31 days after first symptoms. We found that the main T cell response was directed against two specific regions of the spike viral protein, called B and E, which are inversely correlated with the expression of the KIR2DL1 inhibitory receptor on NK cells (p = 0.03, and p = 0.0001 respectively). Furthermore, expression of the inhibitory receptor ILT2 on NK cells was only correlated with T cell responses against the specific E region (p = 0.02), suggesting that HLA-G may play a role in the extinction of the NK response to the T cell response. Moreover, the antibody response was mainly directed against the nucleocapsid, whereas the antibody neutralizing response was inversely correlated with the cellular response to spike (p < 0.003). Taken together these data suggest a strong coordination between the innate and adaptive immune responses during the acute phase of infection, which could reflect the further resolution of COVID-19 patients with severe disease.
Establishing a system to identify correlations among immune system components for exploring alternative pathways for immune information transfer.
Ilan Y
Immunol Lett · 2026 Feb · PMID 40935023 · Publisher ↗
INTRODUCTION: The classic immune system information transfer occurs through direct cell-to-cell contact and the secretion of mediators. However, certain immune phenomena suggest alternative pathways exist between immune...
INTRODUCTION: The classic immune system information transfer occurs through direct cell-to-cell contact and the secretion of mediators. However, certain immune phenomena suggest alternative pathways exist between immune components that operate independently of these conventional mechanisms. METHODS: We used 24 male C57Bl/6 J mice, divided into six groups, to establish a system for testing alternative immune information transfer pathways. Two triggers-splenectomy and 24-hour fasting-were applied in various combinations. Splenocytes were prepared from operated mice and placed in sterile tubes within cages of different treatment groups. Ex vivo lymphocyte responses were measured using fluorescence-activated cell sorting (FACS) for cell epitope expression (CD4, CD8, CD25, Foxp3) and enzyme-linked immunosorbent assay (ELISA) for cytokine secretion (IFN-γ, TNF-α, IL-10, TGF-β). RESULTS: Significant changes were observed in CD25 and CD8+CD25 expression, as well as in IL-10 secretion, following the application of the triggers. The system exhibited inherent variability with trends toward altered immune responses in isolated splenocytes that had no direct contact with the trigger-exposed animals. Non-parametric analysis indicates a trend for these markers, even though there is significant variability within the groups.. CONCLUSIONS: The data suggest a system where correlations between immune components may occur through alternative pathways, indicating the possibility of non-conventional information transfer mechanisms in the immune system that require further investigation.
Analysis of islet antigen-specific autoreactive T cells from Japanese patients with slowly progressive insulin-dependent diabetes mellitus.
Kitagawa N, Kitagawa N, Kobayashi A … +3 more , Okamura T, Hamaguchi M, Fukui M
Immunol Lett · 2026 Feb · PMID 40935022 · Publisher ↗
Pancreatic islet antigen-specific autoreactive T cells are involved in inflammation in slowly progressive insulin-dependent diabetes mellitus (SPIDDM). Pancreatic islet antigens, such as glutamic acid decarboxylase 65 (G...
Pancreatic islet antigen-specific autoreactive T cells are involved in inflammation in slowly progressive insulin-dependent diabetes mellitus (SPIDDM). Pancreatic islet antigens, such as glutamic acid decarboxylase 65 (GAD), insulinoma-associated protein 2 (IA-2), and insulin, are associated with SPIDDM. However, the association between pancreatic islet antigen-specific T cells and SPIDDM incidence remains unclear. We aimed to identify the characteristics of pancreatic islet antigen autoreactive T cells in Japanese patients with SPIDDM. Peripheral blood mononuclear cells were obtained from Japanese patients with type 1 diabetes mellitus (T1DM) enrolled in our diabetic cohort study. An ex vivo cytokine assay using overlapping peptides of GAD, IA-2, and insulin was performed. The production of tumor necrosis factor-alpha (TNF-α) by CD4⁺ T cells and the fractions of TNF-α⁺ CD4⁺ T cell fractions were measured by fluorescence-activated cell sorting. The %parent of TNF-α⁺ CD4⁺ T cells and the effector memory TNF-α⁺ CD4⁺ T cells increased after stimulation with overlapping GAD and IA-2 peptides. The response to overlapping peptides was varied among individual SPIDDM case. Response to overlapping peptides of GAD, IA-2, and insulin were observed in each group of T1DM. Islet antigen-specific autoreactive TNF-α⁺ CD4 T cells from Japanese patients with SPIDDM were activated by overlapping GAD and IA-2 peptides.
Machine learning in allergy research: A bibliometric review.
Kong E, Cucco A, Custovic A … +1 more , Fontanella S
Immunol Lett · 2026 Feb · PMID 40930256 · Publisher ↗
The emergence of big data and analytic approaches initiated research efforts to characterise different subtypes of allergic diseases, including tracking disease progression and identifying patterns that may offer insight...
The emergence of big data and analytic approaches initiated research efforts to characterise different subtypes of allergic diseases, including tracking disease progression and identifying patterns that may offer insight into their development and progression. Triangulation from different data sources and study types may help to elucidate the directionality of relationships between variables at a very individual level by modelling the complex interdependencies between multiple dimensions (e.g., genome, transcriptome, epigenome, microbiome, and metabolome), thereby moving away from associative to a more causal analysis. To ascertain the role of machine learning in allergy research, we conducted a comprehensive systematic review of the current literature. The findings highlight and underscore the potential of using AI/ML approaches in advancing our understanding of allergic diseases, which ultimately enhances patient care through improved prevention, diagnosis, and management strategies. It is important to emphasise that there is no single 'best' analytical method, highlighting the importance of cross-disciplinary collaborations. A team science approach is crucial for ensuring the application of appropriate methodologies tailored to the research question at hand and that context-specific interpretations are being made, supported by critical appraisal from both the front- (e.g., clinicians) and back-end (e.g., analysts) of research processes.
In vitro analysis of azithromycin's effect on J774 murine macrophages challenged with Aspergillus fumigatus.
Antwi I, Fortwendel JR, Cory TJ
Immunol Lett · 2026 Feb · PMID 40925526 · Publisher ↗
BACKGROUND: Patients with chronic lung diseases often suffer from pulmonary aspergillosis, caused by Aspergillus fumigatus (AF). Alveolar macrophages play a key role in the initial immune response to AF. Azithromycin (AZ...
BACKGROUND: Patients with chronic lung diseases often suffer from pulmonary aspergillosis, caused by Aspergillus fumigatus (AF). Alveolar macrophages play a key role in the initial immune response to AF. Azithromycin (AZM), commonly known for its immunomodulatory properties in reducing exacerbations and improving lung function, has mixed effects on the development of aspergillosis. While some studies suggest AZM aids AF-colonized patients, others indicate increased rates of AF colonization. OBJECTIVE: Given AZM's positive impact on host response to other pathogens, we hypothesized that it would improve immune responses to AF by modulating macrophage function. We investigated the in vitro effect of AZM on J774 murine macrophage response to Aspergillus fumigatus. METHOD: The murine macrophage cell line J774 was polarized into distinct phenotypes: (1) classical M1 macrophages, generated using interferon-gamma (IFN-γ) and lipopolysaccharide (LPS); (2) azithromycin-treated M1 macrophages (hereafter referred to as M1A macrophages), generated by treating M1 cells with azithromycin in addition to IFN-γ and LPS; and (3) alternatively activated M2 macrophages, generated using interleukin-4 (IL-4), interleukin-13 (IL-13), and LPS. These polarized macrophages were then analyzed for cytokine production, fungal killing capacity, and reactive oxygen species (ROS) generation. RESULTS: We observed a shift in macrophage phenotype toward an anti-inflammatory-like profile in the AZM-treated group, characterized by an increased fungal killing compared to both M1- and M2-polarized groups. This was accompanied by a reduction in interleukin-6 (IL-6) cytokine production, an increase in arginase activity, without any significant change in ROS generation. Further assays confirmed that the observed increase in fungal clearance was attributable to AZM's impact on macrophages rather than any direct antifungal activity against Aspergillus fumigatus. CONCLUSION: These findings suggest AZM enhances macrophage function, boosting anti-inflammatory responses and improving fungal clearance.
B cell dysregulation during acute COVID-19 is transient.
Jokiranta ST, Nguyen Ngoc A, Huang X … +15 more , Nowlan K, Hannolainen L, Pyöriä L, Pekkarinen PT, Dürnsteiner P, Lääveri T, Heikkilä N, Heinonen S, Laakso SM, Kantele A, Vapalahti O, Strandin T, Hepojoki J, Perdomo MF, Kekäläinen E
Immunol Lett · 2026 Feb · PMID 40915391 · Publisher ↗
BACKGROUND: COVID-19 is still a significant health concern worldwide. B cell responses to COVID-19 have been extensively studied in acute severe disease, but less so during extended follow-up or mild disease. Persisting...
BACKGROUND: COVID-19 is still a significant health concern worldwide. B cell responses to COVID-19 have been extensively studied in acute severe disease, but less so during extended follow-up or mild disease. Persisting immunological changes together with herpesvirus reactivations during acute COVID-19 have been suggested as contributing factors for post-acute sequelae of COVID-19 (PASC). Here, we evaluated the natural kinetics of B cell subpopulations together with serological markers of increased B cell activity during acute COVID-19 and long-term follow-up. We also measured human herpesvirus reactivations during acute COVID-19. METHODS: We collected plasma and peripheral blood mononuclear cell samples from 120 SARS-CoV-2 positive patients (outpatients = 56, inpatients = 64) at up to five timepoints during acute disease and recovery (up to 460 days since symptom onset, dsso). We determined circulating B cell and Th cell subpopulations using flow cytometry, and measured free light chains, in addition to Epstein-Barr virus (EBV) serology, and herpesvirus qPCR from the plasma samples. The presence of anosmia as a proxy for PASC was self-reported at 3-12 months post-COVID. RESULTS: All changes in B cell subpopulation proportions normalized within 200 dsso. Likewise, the acute alterations observed in circulating T follicular helper and T follicular regulatory cell proportions stabilized soon after. Free light chains were high in acute COVID-19, especially in inpatients, but normalized during follow-up. EBV and human herpesvirus 6B (HHV-6B) reactivations were significantly more common in inpatients than outpatients, with reactivation in 47 and 19 % of inpatients and 4.3 and 0 % of outpatients respectively. Anosmia was not significantly associated with any herpesvirus reactivation. CONCLUSIONS: The circulating B cell and Th cell subpopulations experience transitional changes during SARS-CoV-2 infection, but these changes recover in follow-up. EBV and HHV-6B reactivations are common in inpatients, but they are not associated with persisting anosmia.
Importance of BCG Vaccination at birth in Pediatric Patients with Chronic Granulomatous Disease after Hematopoietic Stem Cell Transplantation in Developing Countries.
Hamidieh AA, Behfar M, Nejati N … +6 more , Azar SS, Salmanifard Ardestani MT, Malik R, Kashani H, Mohseni R, Jafari L
Immunol Lett · 2026 Feb · PMID 40902675 · Publisher ↗
INTRODUCTION: Recent advances in hematopoietic stem cell transplantation (HSCT) have improved clinical outcomes; however, various factors continue to influence HSCT success, especially vaccination in immunocompromised pa...
INTRODUCTION: Recent advances in hematopoietic stem cell transplantation (HSCT) have improved clinical outcomes; however, various factors continue to influence HSCT success, especially vaccination in immunocompromised patients who receive vaccination at birth. While several studies have investigated the efficacy of vaccines in Chronic Granulomatous Disease (CGD) patients, the specific impact of vaccination on HSCT outcomes in these patients has not yet been studied. This study aimed to address an important gap in the current literature by investigating the effects of BCG vaccination on HSCT outcomes in patients with CGD. PARTICIPANTS AND METHODS: In this prospective study, 24 pediatric patients with CGD were enrolled from 2016 to 2022, all of whom received the same reduced-intensity conditioning (RIC) regimen before HSCT. Of these, 12 patients received the Bacillus Calmette-Guérin (BCG) vaccine, while 14 patients were not vaccinated. RESULTS: Contrary to other studies, our results showed that CGD patients who received the BCG vaccine before HSCT experienced varying degrees of BCGosis and BCGitis. Specifically, 8 patients showed symptoms of BCGosis, while 4 patients showed symptoms of BCGitis. In addition, our findings revealed no significant differences in graft-versus-host disease (GvHD) and other complications of HSCT between BCG-vaccinated and non-BCG-vaccinated CGD patients, although the overall survival (OS) rate was lower in the vaccinated group. This may be attributed to the reduced-intensity conditioning regimen applied to all patients which can balance HSCT outcome in CGD patients. DISCUSSION AND CONCLUSION: Our study emphasizes the importance of screening and diagnosing immunodeficient patients at birth, especially in developing countries where BCG vaccine is administered at birth, as post- vaccination complications can significantly affect HSCT outcomes and subsequent treatments. BCG vaccination can significantly affect HSCT outcomes and subsequent treatments.
Gut microbiota analysis revealed unique biomarkers in Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis.
Chang S, Chen M, Niu P … +1 more , Zhang J
Immunol Lett · 2026 Feb · PMID 40897216 · Publisher ↗
OBJECTIVES: In this paper, the different characteristics of gut microbiota between Ankylosing Spondylitis (AS), Healthy Control (HC), and Non-radiographic Axial Spondyloarthritis (nr-axSpA) were studied. The AS-nr-axSpA...
OBJECTIVES: In this paper, the different characteristics of gut microbiota between Ankylosing Spondylitis (AS), Healthy Control (HC), and Non-radiographic Axial Spondyloarthritis (nr-axSpA) were studied. The AS-nr-axSpA differentiation model was constructed to identify patients with these two phenotypes and help doctors make accurate diagnosis. METHODS: Stool samples and blood samples of AS, nr-axSpA, and HC were collected from our hospital. Bacterial lipopolysaccharides and lipopolysaccharides-binding proteins in blood were detected by enzyme-linked immunosorbent assay (ELISA). The V3-V4 region of bacterial 16SrRNA was analyzed by MiSeq PE300 sequencing platform with high throughput. Software such as QIIME, R, Excel, etc. were used for statistical analysis of the data. Random Forest (RF) and Area Under Curve (AUC) methods were used to construct the AS-nr-axSpA differentiation model and identify relevant important markers. Set markers and use the receiver operating characteristic curve (ROC) to judge the accuracy of the model. RESULTS: We studied a total of 59 fecal and corresponding blood samples from 31 AS, 21 nr-axSpA, and 7 HC. There was a significant difference in intestinal α diversity between AS and nr-axSpA patients (Shannon index, P = 0.017). Compared to the nr-axSpA patient population, Streptococcus (P = 0.045), Actinomyces (P = 0.0028), Rothia (P = 0.042), and Oribacterium in the intestinal tract of AS patients P = 0.044) increased significantly. However, Dorea (P = 0.034) and Odoribacter (P = 0.043) were significantly reduced. The AS-nr-axSpA model was constructed using 18 factors including Actinomyces and Odoribacter. ROC analysis was performed on the model and an ROC curve was drawn, with an AUC of 0.78, which is moderate accurate. CONCLUSIONS: The gut microbiota of patients with AS differs from that of patients with nr-axSpA. The disturbance of gut microbiota may be one of the conditions for the progression of nr-axSpA to AS. The characteristics of gut microbiota and related bacterial products may serve as characteristic factors for differentiating the phenotypes of these two diseases. The AS-nr-axSpA model may help doctors distinguish patients with different phenotypes, but more robust prospective and standardized studies are needed to confirm these findings.
B cells in inflammatory bowel disease.
Castillo FA, Kern BC, Villablanca EJ
Immunol Lett · 2026 Feb · PMID 40845931 · Publisher ↗
Inflammatory bowel diseases (IBD) have traditionally been considered T cell-driven disorders; however, accumulating evidence challenges this view and underscores a critical, multifaceted role for B cells in the pathogene...
Inflammatory bowel diseases (IBD) have traditionally been considered T cell-driven disorders; however, accumulating evidence challenges this view and underscores a critical, multifaceted role for B cells in the pathogenesis of chronic intestinal inflammation. In the healthy gut, B cells contribute to immune tolerance and mucosal protection primarily through the production of secretory IgA and the regulation of the microbiota. During IBD, the B cell compartment is markedly altered, characterized by increased infiltration of IgA and IgG-secreting PCs, altered humoral responses against gut microbiota and self-antigens, the formation of tertiary lymphoid structures and the emergence of pro-inflammatory subsets such as interferon-induced Sca1⁺PD-L1⁺ B cells. Experimental models have demonstrated both pathogenic and regulatory roles for B cells, which may explain the limited efficacy of pan-B cell depleting therapies, such as rituximab, in clinical settings. This review highlights the evolving landscape of B cell biology in IBD, emphasizing the need for selective therapeutic approaches that distinguish between protective and pathogenic B cells. A deeper understanding of the spatial, phenotypic, and temporal dynamics of intestinal B cell subsets may facilitate the development of precise immunotherapies in IBD.
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