Immunology Letters[JOURNAL]
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200 papers
Th1 recruitment in atopic dermatitis is due to suppression rather than amplification of Th2.
Horiuchi Y
Immunol Lett · 2026 Jul · PMID 42398772 · Publisher ↗
Abstract loading — click title to view on PubMed.
Interleukin-6: A Potential Link in the Pathophysiology of Restless Legs Syndrome.
Kalkman HO, Smigielski L
Immunol Lett · 2026 Jul · PMID 42392513 · Publisher ↗
Iron deficiency, but also iron overload (as observed in Friedreich's ataxia), are associated with an increased prevalence of restless legs syndrome (RLS). However, the pathophysiological mechanisms by which these conditi...
Iron deficiency, but also iron overload (as observed in Friedreich's ataxia), are associated with an increased prevalence of restless legs syndrome (RLS). However, the pathophysiological mechanisms by which these conditions are linked to RLS remain unknown. Here, we propose that elevated circulating levels of interleukin-6 (IL-6) may represent a common underlying factor linking changes in iron homeostasis to the development of RLS. Peripheral IL-6 affects systemic iron distribution, central dopamine synthesis, and sensory neuron sensitivity, thereby contributing to the motor and sensory manifestations of RLS. We suggest that IL-6-mediated signaling may represent a potential therapeutic target for RLS.
The dendritic cell identity crisis: Why do conflicting classifications demand a consensus framework?
Souza-Silva GA
Immunol Lett · 2026 Jun · PMID 42373012 · Publisher ↗
The advent of single-cell technologies has provided unprecedented resolution of dendritic cell (DC) heterogeneity, yet it has paradoxically fueled conceptual fragmentation and conflicting nomenclatures. The field is curr...
The advent of single-cell technologies has provided unprecedented resolution of dendritic cell (DC) heterogeneity, yet it has paradoxically fueled conceptual fragmentation and conflicting nomenclatures. The field is currently divided by divergent models of conventional type 2 DC (cDC2) ontogeny and the debated identity of the DC3 subset, whether it constitutes a distinct hematopoietic lineage or a transient activation state. In this Perspective, I critically analyze these conflicting classifications, focusing on the cDC2A/DC2A developmental dichotomy and the integration of newly described populations such as transitional DC-derived DC2s (tDC2s). I emphasize that these disputes extend beyond semantics, profoundly impacting our mechanistic understanding of disease and therapeutic targeting, as evidenced by the distinct roles of pro-DC3s in viral myocarditis and tDC2s in immune tolerance. I argue that the immunology community urgently requires a consensus framework based on rigorous ontogenetic and functional criteria to harmonize DC classification and translate high-resolution mapping into actionable clinical insights.
The malignancy within: what cancer teaches us about human bonds.
Andrade BB, Araújo-Pereira M
Immunol Lett · 2026 Jun · PMID 42336248 · Publisher ↗
Cancer is a disease of the self. Unlike infectious threats that come from outside, malignancies arise from within, when ordinary cells abandon their cooperative roles and pursue unchecked proliferation. This betrayal of...
Cancer is a disease of the self. Unlike infectious threats that come from outside, malignancies arise from within, when ordinary cells abandon their cooperative roles and pursue unchecked proliferation. This betrayal of biological solidarity offers profound metaphors for understanding interpersonal and social dysfunction. Drawing on the "hallmarks of cancer," the concept of the tumor microenvironment, and advances in immunotherapy, this essay argues that cancer mirrors many relational pathologies: the violation of boundaries, exploitation of shared resources, the masking of harm, and the spread of dysfunction across contexts. Just as tumors evade immune surveillance and exploit systemic vulnerabilities, individuals and groups in social systems manipulate tolerance and exploit complicity. Yet cancer biology also offers lessons in resilience. Therapies reveal the importance of precise, context-sensitive intervention; the biology of remission emphasizes the possibility of repair without erasure. By reflecting on malignancy as metaphor, we see that the health of human relationships requires balance between growth and restraint, vigilance and tolerance, repair and prevention. Cancer thus becomes a biomedical frontier and an ethical and social teacher, offering insights into how individuals and communities can recognize, contain, and heal the malignant dynamics that arise from within.
Progranulin enhances complement component 5a-primed neutrophil activation in antineutrophil cytoplasmic antibody-associated vasculitis.
Lu YY, Chen XY, Lv TG … +1 more , Hao J
Immunol Lett · 2026 Jun · PMID 42331256 · Publisher ↗
BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disorder characterized by vascular inflammation and the activation of neutrophils. Complement component 5a (C5a)...
BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disorder characterized by vascular inflammation and the activation of neutrophils. Complement component 5a (C5a) is pivotal in neutrophil priming and ANCA-mediated activation. Although progranulin (PGRN) is recognized for its involvement in inflammatory processes, yet its specific role in ANCA-associated vasculitis (AAV) remains poorly understood This study investigates the functional interplay between PGRN and C5a in enhancing neutrophil activation in response to ANCA stimulation. METHODS: Neutrophils were primed with recombinant PGRN and subsequently stimulated with myeloperoxidase (MPO)-ANCA or proteinase 3 (PR3)-ANCA-positive immunoglobulin G. The respiratory burst was evaluated through dihydrorhodamine oxidation, while degranulation was quantified by measuring lactoferrin release. Additionally, the effects of PGRN-neutralizing antibodies on C5a-primed neutrophils were evaluated. RESULTS: PGRN significantly upregulated membrane-bound proteinase 3 expression in neutrophils compared to untreated controls (368.0 ± 18.5 vs. 178.0 ± 14.7, p < 0.001) and enhanced MPO release in the culture supernatants (1462.8 ± 202.2 vs. 526.8 ± 118.8, p < 0.001). PGRN-primed neutrophils demonstrated increased respiratory burst activity (p < 0.001) and elevated lactoferrin release (p < 0.001) compared to non-primed cells. Inhibition of PGRN significantly diminished ANCA-mediated oxygen radical production (p < 0.001) and degranulation (p < 0.001) in C5a-primed neutrophils. CONCLUSIONS: PGRN functionally enhances C5a-mediated neutrophil activation, suggesting a cooperative effect but not a direct molecular interaction. This in vitro study using human neutrophils explores the cooperative effects of PGRN and C5a in ANCA-induced activation. Future research should investigate the use of PGRN inhibitors to mitigate inflammation in AAV.
The newly identified role of TRIM72, an E3 ligase, in NINJ1-mediated plasma membrane rupture: focus on its anti-inflammatory function.
Berkel C
Immunol Lett · 2026 Jun · PMID 42297154 · Publisher ↗
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The subsets of circulating follicular helper T cells play an important role in the pathogenesis of Autoimmune thyroid diseases.
Takada S, Inoue N, Iwatani Y … +3 more , Arakawa Y, Hidaka Y, Watanabe M
Immunol Lett · 2026 Jun · PMID 42276259 · Publisher ↗
Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's disease (HD), are thyroid-specific autoimmune diseases; however, predicting prognosis is difficult. Follicular helper T (Tfh) cells play...
Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's disease (HD), are thyroid-specific autoimmune diseases; however, predicting prognosis is difficult. Follicular helper T (Tfh) cells play a critical role in the differentiation of B cells and can be divided into three distinct subsets (Tfh1, Tfh2, and Tfh17), each with different abilities to regulate B cell responses. To elucidate the roles of circulating Tfh cells in the pathogenesis and prognosis of AITDs, we determined their proportions in the peripheral blood of patients with AITD and genotyped single-nucleotide variants (SNVs) in the CXCR5 gene. The proportion of circulating Tfh1 cells in Tfh cells was significantly higher in patients with GD and HD compared with control subjects. In contrast, the proportion of circulating Tfh2 cells was significantly lower in patients with GD and HD compared with control subjects. The G allele of CXCR5 SNV3 was significantly more frequent in patients with severe HD compared with those with mild HD. Overall, increased circulating Tfh1 cells and decreased circulating Tfh2 cells may play an important role in the pathogenesis of AITDs. The G allele of CXCR5 SNV3 may have a role in HD severity.
Could bradykinin pathway inhibition change the course of severe hantavirus disease?
Weerheim M, Karim F
Immunol Lett · 2026 Jun · PMID 42251906 · Publisher ↗
A recent multi-country hantavirus outbreak associated with a cruise ship underscores the urgent need to understand the mechanisms driving severe vascular leakage and multi-organ failure. While disease severity is largely...
A recent multi-country hantavirus outbreak associated with a cruise ship underscores the urgent need to understand the mechanisms driving severe vascular leakage and multi-organ failure. While disease severity is largely attributed to a dysregulated host immune response and intense cytokine surge, the precise molecular mediators remain incompletely defined. Laboratory evidence indicates that hantavirus infection activates the factor XII-dependent kallikrein-kinin system, leading to elevated bradykinin production and subsequent endothelial barrier dysfunction. This translational mechanism is tentatively supported by two clinical case reports where severe hantavirus infections were successfully treated with the bradykinin receptor antagonist icatibant. We hypothesize that exaggerated bradykinin signalling drives the vascular leak phenotype, making the kallikrein-kinin pathway a compelling therapeutic target. Ultimately, effectively combating hantavirus-induced vascular permeability may require a multi-faceted approach combining targeted bradykinin inhibition with broader immunomodulatory strategies.
Lactate-related diagnostic signature in rheumatoid arthritis: WGCNA and LASSO analysis with experimental validation.
Jiang Y, Sun C, Yu Q … +2 more , Liu H, Ding Y
Immunol Lett · 2026 Jun · PMID 42251905 · Publisher ↗
BACKGROUND: Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. Accumulating evidence reveals that lactate plays a vital role in progression of RA. This study aimed to identify lactate-related gene...
BACKGROUND: Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. Accumulating evidence reveals that lactate plays a vital role in progression of RA. This study aimed to identify lactate-related genes (LRGs) associated with RA and investigate their potential pathological correlation with immune-infiltrating cells and their potential as diagnostic markers in RA. METHODS: We downloaded four RA-related datasets containing 51 RA and 36 healthy synovium samples from the Gene Expression Omnibus (GEO) database and extracted the expression profiles of lactate-related genes to identify differentially expressed genes (DEGs). Subsequently, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) were employed to identify the hub genes for RA diagnosis. Receiver operating characteristic (ROC) curves were used to validate the specificity and sensitivity of the hub genes. Additionally, we analyzed the infiltration levels of 28 immune cells in the expression profiles and their relationship with the hub genes using single-sample gene set enrichment analysis. Finally, the expression levels and function of hub genes were verified. RESULTS: We identified 373 differentially expressed LRGs (232 upregulated and 141 downregulated genes) between RA and healthy controls. WGCNA and LASSO analysis results identified TPK1 and IBA57 as potential diagnostic biomarkers for RA. The combination of the two hub genes showed great diagnostic ability (AUC > 0.8) in multiple independent validation dataset. Additionally, IBA57 may involved in the immune mechanism of DC cells, whereas TPK1 may be involved in regulating macrophage function in the immune response to RA. Also, TPK1 is highly expressed in RA, and knockdown TPK1 attenuated RA-FLS invasion and migration. CONCLUSIONS: These data indicate that lactate-related gene TPK1 and IBA57 are valuable diagnostic biomarkers for RA and are closely associated with immune cell infiltration, and TPK1 may play an important role in RA progression. These findings provide new insights into the pathogenesis of RA and potential diagnostic targets.
Precise sequential combination of cisplatin and cyclophosphamide induces higher anti-tumor and immunomodulatory effects against experimental Ehrlich ascites.
Salem ML, Khalil SM, El Shahry ST … +1 more , Mourad SS
Immunol Lett · 2026 Jun · PMID 42251904 · Publisher ↗
BACKGROUND: Cisplatin (CIS) and cyclophosphamide (CTX) are commonly used in clinical oncology, often in combination to improve therapeutic outcomes. However, most preclinical studies have examined these agents individual...
BACKGROUND: Cisplatin (CIS) and cyclophosphamide (CTX) are commonly used in clinical oncology, often in combination to improve therapeutic outcomes. However, most preclinical studies have examined these agents individually, overlooking the potential synergistic and immunomodulatory effects of combined treatment. This study aimed to compare the antitumor and immune-modulating effects of single versus combined CTX and CIS chemotherapy, and to determine the treatment sequence that achieves maximum efficacy with minimal toxicity. METHODS: Adult female mice (n = 5/group) were inoculated intraperitoneal (i.p.) with 0.5 × 10⁶ fresh viable Ehrlich ascites carcinoma (EAC) cells. Twenty-four hours' post-inoculation, animals received a single administration of phosphate-buffered saline (PBS), CIS, CTX, or various combinatorial CIS-CTX regimens. Antitumor activity and alterations in myeloid cell subsets, including dendritic cells (DCs), monocytes, and neutrophils, were evaluated in peripheral blood and spleen by flow cytometry. RESULTS: EAC-bearing mice showed changes in splenic and circulating immune cell populations based on CD11c and CD11b expression profiles, suggesting tumor-associated immunomodulatory alterations. CIS and CTX monotherapy partially restored myeloid cell populations. Notably, sequential regimens, particularly CIS followed by escalating doses of CTX-led to substantial increases in both mature neutrophils and plasmacytoid DCs (pDCs), while reducing CD11b myeloid cell population associated with immunosuppressive phenotypes. These changes suggest enhanced myelopoiesis and innate immune activation in treated mice. CONCLUSIONS: A regimen consisting of high-dose CTX combined with low-dose CIS demonstrated robust anti-tumor activity while limiting leukopenia and systemic toxicity. This protocol may represent an optimal therapeutic strategy, balancing efficacy with safety.
Aerobic exercise attenuates airway inflammation in allergic asthma by regulating M2 macrophage polarization via drp1-mediated mitophagy.
Ding L, Wu N, Lin J
Immunol Lett · 2026 Jun · PMID 42251903 · Publisher ↗
Allergic asthma is a chronic respiratory condition characterized by persistent airway inflammation and dysregulated macrophage activation. Although aerobic exercise is known to exert anti-inflammatory effects, its influe...
Allergic asthma is a chronic respiratory condition characterized by persistent airway inflammation and dysregulated macrophage activation. Although aerobic exercise is known to exert anti-inflammatory effects, its influence on macrophage polarization and mitochondrial dynamics in asthma remains poorly defined METHODS: Using a rat model of ovalbumen (OVA)-induced allergic asthma, we investigated the impact of aerobic exercise on macrophage polarization and mitophagy regulation. Animals were divided into four experimental groups: control, OVA-induced asthma, OVA with aerobic exercise intervention, and OVA with Drp1 inhibitor (Mdivi-1) treatment. We evaluated airway inflammation, macrophage phenotypes, mitochondrial function, and key mitophagy-related proteins RESULTS: Aerobic exercise significantly attenuated allergic airway inflammation, as evidenced by reduced inflammatory cell infiltration, decreased mucus production, and a shift in macrophage polarization from the M2 towards the M1 phenotype. At the molecular level, exercise suppressed mitophagy activation, reduced Drp1 phosphorylation, and downregulated the expression of mitophagy-related proteins. These effects were mirrored by Drp1 inhibition with Mdivi-1, confirming the crucial role of Drp1-mediated mitophagy in exercise-induced modulation of macrophage polarization CONCLUSION: Our findings indicate that aerobic exercise alleviates allergic airway inflammation by inhibiting Drp1-dependent mitophagy and rebalancing macrophage polarization. These results provide novel mechanistic insights into the therapeutic potential of exercise in asthma and highlight mitophagy as a promising target for inflammatory respiratory diseases.
Characterization of innate immune cells with regulatory functions in subjects with a remote history of Kawasaki disease who lack natural regulatory T cell specificities.
Song J, Ruedas Montero RE, Hernandez SY … +3 more , Tremoulet AH, Burns JC, Franco A
Immunol Lett · 2026 Jun · PMID 42242631 · Publisher ↗
Kawasaki disease (KD) is an acute pediatric vasculitis of the coronary arteries. In the acute phase, natural regulatory T cells (nTreg) that recognize peptides of the heavy constant region of IgG (Fc), an important nTreg...
Kawasaki disease (KD) is an acute pediatric vasculitis of the coronary arteries. In the acute phase, natural regulatory T cells (nTreg) that recognize peptides of the heavy constant region of IgG (Fc), an important nTreg specificity in humans, are poorly expanded. Intravenous immunoglobulin therapy (IVIG) restores the expansion of Fc-specific nTreg, by providing high concentrations of Fc. However, Fc-specific nTreg wane over time, shortly after IVIG. Here we explored the mechanism that prevents the undesirable activation of pro-inflammatory T cells in healthy subjects with a remote history of KD, studied years after IVIG. Indeed, we characterized several innate immune cells that secreted two suppressive cytokines, interleukin-1 receptor antagonist (IL-1Ra) and IL-10. When studied side-by-side with healthy controls, we did not find differences within the immune monitoring between the two cohorts. Of interest, classical monocytes were activated and expanded in an Fc-dependent manner, secreted IL-1Ra and IL-10, and polarized toward regulatory DC. The results suggested that IgG concentrations play a role in the differentiation of monocytes, unveiling a mechanism for immune regulation.
No expansion of MIS-c associated TCR Vβ 21.3 T-cells in pediatric Post-COVID condition.
Tulling AJ, Holierhoek MG, van der Kroft SN … +5 more , van Ostaijen-Ten Dam MM, van Houten MA, Terheggen-Lagro SWJ, Lugthart G, Buddingh EP
Immunol Lett · 2026 Jun · PMID 42235853 · Publisher ↗
The etiology of pediatric post-COVID Condition (PPCC; i.e., long-COVID) remains elusive. Another post-infectious complication of SARS-CoV-2 in children is Multisystem Inflammatory Syndrome in Children (MIS-C) in which an...
The etiology of pediatric post-COVID Condition (PPCC; i.e., long-COVID) remains elusive. Another post-infectious complication of SARS-CoV-2 in children is Multisystem Inflammatory Syndrome in Children (MIS-C) in which an expansion of polyclonal TCR Vβ 21.3 (TRBV11-2) T-cells has been observed. Flow cytometry was performed in 86 PPCC, 32 MIS-C, 7 pediatric acute COVID-19, and 15 age matched healthy controls. Most children with MIS-C (25/32, 78%) had an enrichment of Vβ21.3 expressing cells within activated HLA-DR/Ki67 T-cells. In contrast to children with MIS-C, there was no enrichment of Vβ21.3 expressing cells in PPCC patients, arguing against a shared pathophysiology.
The vimentin-targeting monoclonal antibody hzVSF-V13 reduces TH17 cell numbers and osteoclastogenesis to attenuate rheumatoid arthritis progression.
Lee AR, Choi H, Lee SY … +3 more , Choi JW, Han SG, Cho ML
Immunol Lett · 2026 May · PMID 42219042 · Publisher ↗
BACKGROUND: In an inflammatory environment, damage to vimentin (Vim) can induce its citrullination. Together with the formation of immune complexes, citrullinated Vim further stimulates inflammatory processes, leading to...
BACKGROUND: In an inflammatory environment, damage to vimentin (Vim) can induce its citrullination. Together with the formation of immune complexes, citrullinated Vim further stimulates inflammatory processes, leading to chronic inflammation. Patients with rheumatoid arthritis (RA), an autoimmune disease, have elevated levels of anti-citrullinated Vim antibodies. METHODS: Therefore, we aimed to demonstrate the effects of a Vim-targeting IgG4 monoclonal antibody in RA. hzVSF-V13 treatment reduced arthritis severity and induced immunoregulatory effects, as indicated by a reduction in Th17 cells and pro-inflammatory cytokines. RESULTS: Decrease in citrullinated Vim-specific IgG levels in serum were accompanied by a decrease in citrullinated Vim in joint tissue. Also, it reduced the expression of osteoclast differentiation factors in RA patient samples. CONCLUSIONS: These results suggest the ability of hzVSF-V13 to suppress inflammation and osteoclast differentiation not only in an animal model of collagen-induced arthritis, but also in RA patients. The clinical application of hzVSF-V13 may lead to effective treatment of RA patients.
Cardiac surgery modulates leucocyte subsets and inflammatory mediators.
Perros AJ, Rooks K, Chong F … +12 more , Engkilde-Pedersen S, Esguerra-Lallen A, Hewlett E, Faddy HM, Naidoo R, Tung JP, Fraser JF, Tesar P, Ziegenfuss M, Smith SE, Flower RL, Dean MM
Immunol Lett · 2026 Aug · PMID 42144144 · Publisher ↗
Leucocytes regulate the immune response through multiple pathways including cytokine release, which is critical for mediating host defences. Coronary artery bypass grafting (CABG) initiates a systemic inflammatory respon...
Leucocytes regulate the immune response through multiple pathways including cytokine release, which is critical for mediating host defences. Coronary artery bypass grafting (CABG) initiates a systemic inflammatory response that may contribute to adverse patient outcomes. Full blood counts (FBC) provide insight into patient's haematological status, however FBC don't provide comprehensive analysis of leucocyte subsets. We investigated the impact of CABG on circulating leucocyte subsets and plasma cytokine levels. Whole blood was collected from CABG patients (n = 75) at five time-points (admission, intra-operative, ICU, day three (D3), day five (D5)). The absolute count of monocytes, natural killer (NK) cells, B-cells, T-cell subsets, and dendritic cell (DC) subsets were assessed using Trucount tubes. A full blood count was performed on each patient sample and used to calculate the lymphocyte monocyte ratio and neutrophil lymphocyte ratio. Cytokine levels in patient plasma were measured via cytometric bead array. The relationship between CABG-associated immunomodulation and patient outcomes (atrial fibrillation (AF) and ICU length of stay (LOS)) was also explored. Compared to admission, patient monocyte numbers increased, and T-cell numbers decreased from the ICU period. B-cell numbers initially decreased during CABG surgery before increasing from D3. During the CABG procedure, classical DC numbers decreased, while plasmacytoid DC numbers increased. CABG also increased plasma levels of IL-6, MCP-10 and IP-10. Modulation of DC subsets, DC subset activation markers and T-cell subsets were associated with AF and ICU LOS. This study demonstrates the utility of comprehensive leucocyte subset and ratio analyses in CABG patients and provides further insight into cardiac immunobiology. Detailed assessment of the patient haematological status could be used as a clinical tool to guide post-operative management.
Elevated cytokine and nitric oxide levels in Behçet disease: EBI-3 as a potential biomarker of vascular involvement.
Ghozali N, Hadjimi Z, Abdesselam Z … +10 more , Bouzid F, Ihammichene S, Kediha MI, Terahi M, Belkacem HAA, Hakem D, Moulay S, Laraba N, Touil-Boukoffa C, Belguendouz H
Immunol Lett · 2026 May · PMID 42144143 · Publisher ↗
BACKGROUND: Behçet disease (BD) is multisystem inflammatory vasculitis affecting vessels of all types and sizes. Vascular involvement represents one of the most severe and life-threatening manifestations, associated with...
BACKGROUND: Behçet disease (BD) is multisystem inflammatory vasculitis affecting vessels of all types and sizes. Vascular involvement represents one of the most severe and life-threatening manifestations, associated with increased morbidity and mortality. The aim of this study was to investigate the role of cytokines and nitric oxide (NO) in the pathogenesis of BD, which could potentially highlight a new biomarker, capable of discriminating between patients with and without vascular involvement. METHODS: Plasma levels of cytokines and NO were measured using ELISA and modified Griess method, respectively. Statistical analyses were performed using Mann Whitney U test and Kruskal-Wallis for group comparisons. RESULTS: Our results demonstrated a significant increase in EBI-3 levels in patients with vascular involvement compared to both non-vascular patients and healthy controls (HC). Receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.8901± 0.07705 (0.7391 to 1.000). At a cutoff value of 56.56 pg/ml, EBI-3 showed a specificity of 92.86% and a sensitivity of 84.62% (P = 0.0006). In contrast, NO, IL-6 and IL-32 levels were significantly elevated in all BD clinical manifestations compared to HC. While, IL-6R, IL-10, and IL-37 showed no significant difference. CONCLUSION: These findings highlight the potential involvement of EBI-3 in vascular manifestations and suggest its utility as a biomarker for vascular involvement of BD.
Disrupting adenosine triphosphate metabolism as a therapeutic strategy against lymphatic cancer progression: a review.
Qutub M, Premchandani T, Faizan M … +6 more , Tatode A, Khan R, Taksande J, Umekar M, Singh M, Sharma P
Immunol Lett · 2026 May · PMID 42142542 · Publisher ↗
Adenosine triphosphate (ATP), the universal cellular energy currency, functions as a central regulator of cancer progression beyond its classical bioenergetic role. This review integrates current evidence on how dysregul...
Adenosine triphosphate (ATP), the universal cellular energy currency, functions as a central regulator of cancer progression beyond its classical bioenergetic role. This review integrates current evidence on how dysregulated ATP metabolism and signaling contribute to lymphatic cancer progression. Cancer cells undergo metabolic reprogramming, including enhanced glycolysis, fatty acid oxidation (FAO), and oxidative phosphorylation, to sustain elevated ATP production required for proliferation, invasion, and metastasis. ATP plays a pivotal role in lymph node metastasis (LNM), where tumor-derived factors reprogram lymphatic endothelial cells to increase FAO-dependent ATP generation, thereby promoting lymphangiogenesis. Extracellular ATP (eATP) further contributes to tumor progression by activating purinergic receptors, which enhance cancer cell migration and invasiveness. Within the tumor microenvironment (TME), eATP exhibits a dual role. As a damage-associated molecular pattern released during immunogenic cell death, it can stimulate anti-tumor immune responses through dendritic cell activation. However, its rapid hydrolysis by ectonucleotidases CD39 and CD73 produces adenosine, leading to immunosuppression, T-cell exhaustion, and the establishment of an immune-evasive niche, particularly in tumor-draining lymph nodes. ATP-dependent mechanisms also underlie chemoresistance, primarily via ATP-binding cassette (ABC) transporters that actively efflux chemotherapeutic agents. Additionally, the overexpression of ATP-related metabolic enzymes and transporters, including ATP synthase and ATP-citrate lyase (ACLY), correlates with advanced disease stage, metastasis, and poor prognosis. Collectively, ATP-driven pathways represent a critical nexus linking metastasis, immune modulation, and therapeutic resistance, offering promising avenues for biomarker development and targeted therapeutic strategies.
Previous administration of recombinant or wild type Lactococcus lactis NCDO2118 prevented severe mucositis in mice.
de Barros PAV, Pinheiro-Rosa N, Miranda MCG … +13 more , Alves JL, Espaladori MC, Assis HC, Júnior REM, Pessoa RM, Veloso ES, Vieira AT, Brunialti-Godard AL, Cardoso VN, Ferreira E, Azevedo VAC, Maioli TU, Faria AMC
Immunol Lett · 2026 May · PMID 42134477 · Publisher ↗
Mucositis is an inflammatory ulcerative condition that affects the mucous membranes of the entire gastrointestinal tract caused by anti-cancer chemotherapy. In the search for strategies to prevent or control this conditi...
Mucositis is an inflammatory ulcerative condition that affects the mucous membranes of the entire gastrointestinal tract caused by anti-cancer chemotherapy. In the search for strategies to prevent or control this condition,many probiotic bacteria have been described as promising therapeutic tools. However, giving live bacteria during gut inflammatory conditions is a clinical concern and preventive treatments are the most suitable design namely when the disease onset is known as in the case of chemotherapy-induced mucositis. In the present study, we tested the effects of Lactococcus lactis NCDO2118 and Hsp65-producing L. lactis as a previous treatment to modulate intestinal mucosa immunity and prevent mucositis. Bacteria were given orally in a water bottle for four days. After ten days of the last treatment day, mucositis was induced. The results showed that pretreatment with either recombinant Hsp65-producing or wild type L. lactis NCDO2118 reduced intestinal permeability, preserved proteins of the junctional complex, and consequently controlled bacteria translocation. Pretreatment prevented the augment of inflammatory cells involved in mucositis pathogenesis, showing reduction in inflammation mediated by a favorable balance between cytokines. Furthermore, treatment of mice with recombinant or wild type L. lactis for four days modulated the gut microbiota contributing to intestinal homeostasis and to mucositis prevention. Together, our data showed that Hsp65-producing L. lactis and wild type L. lactis administered 10 days before disease induction had long-lasting immunoregulatory effects on mucositis. It provides an alternative therapeutic tool for mucositis that would avoid the risk of administering live bacteria during intestinal inflammation.
A novel mutation in the STK4 gene (Serine/threonine kinase 4) in a Chinese Blang child.
Liu Y, Lei Y, Li M … +9 more , Sun Y, Liu X, Zhou Y, Yu J, Min J, Lu J, Liu Q, Li L, Xu Q
Immunol Lett · 2026 Aug · PMID 42119789 · Publisher ↗
BACKGROUND: This study explored the clinical phenotypic characteristics, auxiliary examination findings, and gene mutation features of a patient with an STK4 gene mutation to increase the ability of clinicians to identif...
BACKGROUND: This study explored the clinical phenotypic characteristics, auxiliary examination findings, and gene mutation features of a patient with an STK4 gene mutation to increase the ability of clinicians to identify STK4 deficiency early and provide more targeted guidance for optimizing subsequent diagnosis and treatment protocols to improve patient prognosis. METHODS: We conducted a retrospective analysis of the clinical data and follow‑up information for a patient with an STK4 gene variant and their family members (of the proband) who presented to the Department of Respiratory Medicine, Kunming Medical University Children's Hospital, on August 21, 2024. Whole‑exome sequencing (WES) was used to screen for candidate variants, and Sanger sequencing was employed for family validation. Comprehensive analysis was performed by integrating results from quantitative EBV‑DNA testing, EBV serology, and MetaCAP high‑throughput pathogen nucleic acid sequencing. RESULTS: The patient presented with recurrent infections since early childhood. Ancillary examinations revealed hepatosplenomegaly. Immunological evaluation showed a marked reduction in CD4T cells accompanied by hypogammaglobulinemia. Genetic testing identified a homozygous variant in the STK4 gene: NM_006282.5:c.305T>G (p.M102R). Sanger sequencing confirmed that both parents were heterozygous carriers of this variant, consistent with an autosomal recessive inheritance pattern. Combined with the clinical manifestations, immunological abnormalities, family segregation analysis, and ACMG/AMP criteria, this variant was considered a likely pathogenic variant strongly associated with the patient's phenotype. CONCLUSIONS: This study reports a child with a homozygous variant in the STK4 gene. This case helps deepen the understanding of immune abnormalities associated with STK4 deficiency and underscores the importance of early genetic screening and immunological evaluation to facilitate early diagnosis and individualized management.
Chemokine dynamics after mRNA vaccination.
Marques Palma L, Schlaweck S, Flores C … +5 more , Aslan H, Kurts C, Brossart P, Becker-Gotot J, Heine A
Immunol Lett · 2026 Aug · PMID 42097179 · Publisher ↗
AIMS: Since the COVID-19 pandemic, mRNA-based vaccines have gained prominence and opened up new opportunities for vaccine development. Rapid and long-lasting immune responses to antigens are crucial for the success of va...
AIMS: Since the COVID-19 pandemic, mRNA-based vaccines have gained prominence and opened up new opportunities for vaccine development. Rapid and long-lasting immune responses to antigens are crucial for the success of vaccines. Chemokines, cytokines, and chemokine receptors play an essential role in this process; thus, in this study, we aimed to investigate their regulation and the resulting immune cell profile during mRNA-based SARS-CoV2 vaccination. MAIN METHODS: SARS-CoV-2 neutralizing antibody titers were examined by ELISA. Chemokine abundance before and after 2nd dose of the mRNA-1273 vaccine on time points d-1, d+1/2, d+3/4, and d+7 was examined in serum samples using bead-based immunoassays. In addition, flow cytometric analysis of blood samples was performed to characterize chemokine receptor expression on several immune cell populations associated with vaccination success. KEY FINDINGS: Our results demonstrated that mRNA-1273 vaccination increased serum levels of type 1 (IFNγ), type 2 (IL-4), other pro-inflammatory cytokines (IL-1α, IL-1β) and chemokines (CXCL9, CXCL10, CXCL11, CCL2, CCL4) between day 1 and day 4 post vaccination. Vaccination altered chemokine receptor expression on various cell types. Despite high interindividual differences, enhanced expression was observed for CXCR5 on activated CD4 T cells. Furthermore, CCR5 expression was increased on RBD⁺ B cells after vaccination, while CCR1, CCR2, CCR4, CCR5, and CXCR5 were elevated on different monocyte subsets. A notable finding was the positive correlation between elevated CXCR4 expression on RBD⁺ B cells and a high SARS-CoV-2 neutralizing antibody (NAb) titer ratio. SIGNIFICANCE: We here demonstrate a dynamic, cell-specific chemokine regulation early after mRNA booster vaccination. This chemokine modulation likely facilitates an efficient induction of innate immune cell and adaptive T cell responses.
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