Immunology Letters[JOURNAL]
Sun
200 papers
CD36/ANXA1/TLR4/NF-κB axis orchestrates lipid metabolism, chronic inflammation, and insulin resistance in obese children.
Yao Y, Yang W, Cheng F … +1 more , Mao S
Immunol Lett · 2026 Aug · PMID 42092702 · Publisher ↗
BACKGROUND: Childhood obesity is tightly linked to dyslipidemia, chronic low-grade inflammation, and insulin resistance (IR). CD36 has been implicated in metabolic disease, yet its pediatric mechanisms remain unclear. Th...
BACKGROUND: Childhood obesity is tightly linked to dyslipidemia, chronic low-grade inflammation, and insulin resistance (IR). CD36 has been implicated in metabolic disease, yet its pediatric mechanisms remain unclear. This study aims to investigate the CD36/ANXA1/TLR4/NF-κB axis as a potential therapeutic target for lipid metabolism and IR in childhood obesity. METHODS: A case-control study was conducted involving 50 obese and 50 healthy control children. Clinical data and blood samples were collected to assess metabolic profiles. Primary adipocytes isolated from subcutaneous adipose tissue were used for in vitro experiments. We established CD36 knockdown and overexpression models and performed a range of molecular and cellular assays. These experiments were designed to analyze the effects of CD36 on adipogenesis, insulin signaling, and inflammatory pathways, both with and without the addition of insulin, LPS, or a TLR4-blocking antibody. RESULTS: Compared with controls, children with obesity showed higher BMI, fasting glucose/insulin, TAG, and TC. Circulating levels of soluble CD36 (sCD36) were markedly elevated in plasma, and CD36 expression was increased in adipocytes from obese children, accompanied by enhanced pro-inflammatory cytokine production and reduced GLUT4/IRS1 expression. In primary adipocytes, CD36 overexpression enhanced PPARγ and adipogenesis, whereas CD36 knockdown suppressed lipid accumulation. Mechanistically, CD36 silencing increased AKT phosphorylation and restored GLUT4/IRS1, indicating relief of IR via PI3K/AKT activation. Notably, CD36 physically interacted with ANXA1 and potentiated TLR4/NF-κB signaling. Functionally, LPS reversed anti-inflammatory and anti-adipogenic effects of CD36 knockdown, whereas TLR4 blockade countered CD36-driven cytokine production and adipogenesis. CONCLUSIONS: This study shows the CD36/ANXA1/TLR4/NF-κB axis as a signaling pathway associated with inflammation and lipid metabolism dysregulation in childhood obesity and provides mechanistic evidence that targeting this axis may ameliorate insulin resistance and adipogenesis.
Upregulated Macrophage-Inducible C-Type Lectin on Intermediate Monocytes Facilitates T Helper 17 Cell Differentiation in Systemic Lupus Erythematosus.
Li S, Li J, Xiao Y … +5 more , Guo Y, Sui Y, Zhao ZJ, Zheng Z, Chen Y
Immunol Lett · 2026 Aug · PMID 42069227 · Publisher ↗
Pattern recognition receptors are crucial for autoimmune responses. While C-type lectins play important roles in immune responses, their involvement in systemic lupus erythematosus (SLE) pathogenesis remains less underst...
Pattern recognition receptors are crucial for autoimmune responses. While C-type lectins play important roles in immune responses, their involvement in systemic lupus erythematosus (SLE) pathogenesis remains less understood. To investigate this, we utilized Gene Expression Omnibus data for bioinformatics analyses and obtained peripheral blood samples from SLE patients to study the expression, functions, and potential mechanisms of macrophage-inducible C-type lectin (Mincle). The results indicated that the C-type lectin receptor signaling pathway is involved in SLE initiation, with Mincle mRNA levels significantly upregulated in SLE. Specifically, upregulated Mincle was observed on intermediate monocytes (CD14CD16) from SLE patients. The increased Mincle expression among intermediate monocytes was associated with elevated serum immunoglobulin G and κ-light chain in SLE. Moreover, the intermediate monocytes from SLE promoted T helper 17 (Th17) differentiation. In THP-1 cells, Mincle deficiency reduced the differentiation of CD4 naïve T cells towards Th17, whereas Mincle overexpression in THP-1 and U937 cells facilitated differentiation towards Th1 and Th17. In conclusion, upregulated Mincle on circulating intermediate monocytes facilitates T cell differentiation toward Th17, thereby aggravating systemic inflammation and promoting SLE progression.
FNDC1-driven macrophage polarization promotes breast cancer cell invasion.
Lian B, Yang H, Qin Q … +2 more , Lian S, Wei C
Immunol Lett · 2026 Aug · PMID 42055255 · Publisher ↗
OBJECTIVES: Fibronectin Type III Domain Containing 1 (FNDC1) has been linked to several cancers, but its role in breast cancer and its impact on the tumor microenvironment, particularly macrophage polarization, are poorl...
OBJECTIVES: Fibronectin Type III Domain Containing 1 (FNDC1) has been linked to several cancers, but its role in breast cancer and its impact on the tumor microenvironment, particularly macrophage polarization, are poorly understood. This study investigated FNDC1 expression in breast cancer tissues and its effects on macrophage polarization and tumor progression. METHODS: This cross-sectional study collected breast cancer and adjacent normal tissue samples from 31 patients, and FNDC1 expression levels were analyzed using immunohistochemistry. Data from The Cancer Genome Atlas (TCGA) and the GEPIA databases were further used to validate FNDC1 expression patterns. In vitro experiments were performed using macrophages transfected with an FNDC1-overexpressing lentiviral vector to assess its effects on macrophage polarization. FNDC1 expression was evaluated by qPCR and Western blot, whereas macrophage polarization markers CD80, CD86, CD115 and CD206 were assessed by flow cytometry. Exosomes secreted by FNDC1-overexpressing macrophages were isolated and characterized, and their effects on breast cancer cell migration and invasion were assessed using wound-healing and Transwell assays. In addition, exosomes derived from M0, M1, and M2 macrophages, as well as from PLX3397-treated M2 macrophages, were evaluated in Transwell invasion assays in MCF-7 and MDA-MB-231 cells. RESULTS: FNDC1 expression was significantly higher in breast cancer tissues compared with adjacent normal tissues, as confirmed by immunohistochemistry and validated by TCGA and GEPIA database analyses. Overexpression of FNDC1 in macrophages promoted polarization toward the M2 phenotype, as evidenced by increased expression of CD115 and CD206. Exosomes derived from FNDC1-overexpressing macrophages enhanced the migratory and invasive abilities of breast cancer cells in vitro. Exo-M2 significantly promoted breast cancer cell invasion, whereas exo-M1 reduced invasion, and PLX3397 treatment attenuated the pro-invasive effect of exo-M2. These findings suggest that FNDC1 may contribute to breast cancer progression through macrophage polarization and exosome-mediated modulation of cancer cell behavior. CONCLUSIONS: This study demonstrates that FNDC1 is upregulated in breast cancer tissues and promotes breast cancer cell migration and invasion by promoting M2-like macrophage polarization and enhancing the pro-invasive effects of macrophage-derived exosomes. FNDC1 may serve as a novel therapeutic target for modulating the tumor microenvironment and improving outcomes for breast cancer patients.
RanGAP1 plays a vital role in anti-infective functions of macrophages and sepsis progression.
Mao L, Liu G, Zhang J … +5 more , Zhao Q, Zhang X, Zhang S, Zhang Y, Bai X
Immunol Lett · 2026 Aug · PMID 42055254 · Publisher ↗
Ran GTPase-activating protein 1 (RanGAP1) is a known regulator of nucleocytoplasmic transport; however, its specific function within innate immunity remains undefined. Here, we show that low RanGAP1 expression correlates...
Ran GTPase-activating protein 1 (RanGAP1) is a known regulator of nucleocytoplasmic transport; however, its specific function within innate immunity remains undefined. Here, we show that low RanGAP1 expression correlates with poor survival outcomes in septic patients and demonstrate that RanGAP1 expression and subcellular localization are dynamically regulated in macrophages following lipopolysaccharide (LPS) stimulation. We observed that deletion of RanGAP1 in macrophages exacerbates sepsis progression by using a cecal ligation and puncture (CLP) murine model. Mechanistically, RanGAP1 deficiency significantly impairs macrophage anti-infective functions, including inflammatory cytokine production, pathogen clearance, and antigen processing. These findings highlight RanGAP1 as a central regulator of macrophage immune responses, suggesting that its activity is a critical determinant of septic outcomes.
1995-2025: A long journey in the ALPS.
Rieux-Laucat F
Immunol Lett · 2026 Aug · PMID 41997376 · Publisher ↗
The discovery of heterozygous germline mutations in FAS 30 years ago led to an understanding of the pathophysiology associated with familial forms of autoimmune lymphoproliferative syndrome (ALPS). Ten years later, the i...
The discovery of heterozygous germline mutations in FAS 30 years ago led to an understanding of the pathophysiology associated with familial forms of autoimmune lymphoproliferative syndrome (ALPS). Ten years later, the identification of somatic mutations in FAS was the first description of an acquired mutation in a non-cancerous disease. It was subsequently observed that haploinsufficient germline mutations are accompanied by a somatic mutation in the second FAS allele or by somatic loss of heterozygosity. More recently, germline and combined mutations in FADD have also been described in ALPS. In contrast, mutations in other proteins of the signaling pathway, such as caspases 8 and 10, do not appear to be associated with ALPS. Finally, biallelic mutations in the FAS ligand (FASLG) can also lead to an ALPS phenotype. In all these genetic forms of ALPS, hyperactivation of the mTOR pathway, observed in animal models and subsequently in humans, has demonstrated the efficacy of mTOR inhibitors as a standard treatment for ALPS. Since the discovery of FAS in ALPS, mutations in numerous other genes (CTLA4, LRBA, STAT3) have been described in patients presenting with ALPS symptoms combined with signs of immunodeficiency. It has been proposed to distinguish these monogenic ALPID disorders to avoid confusing them with ALPS, which is specifically associated with a defect in the FASLG/FAS pathway.
Age-dependent variations in circulating Tfh and Tfr cells following SARS-CoV-2 infection.
Velichkov AG, Susurkova RI, Trifonova AI … +7 more , Pasev MD, Tosheva EA, Guenova ML, Stankova ES, Uzunova YG, Qu X, Terzieva VI
Immunol Lett · 2026 Aug · PMID 41980656 · Publisher ↗
Studies of the COVID-19 pandemic revealed differences in the clinical course between paediatric and adult patients. In-depth research on whether T follicular cells support these observations is still ongoing. Circulating...
Studies of the COVID-19 pandemic revealed differences in the clinical course between paediatric and adult patients. In-depth research on whether T follicular cells support these observations is still ongoing. Circulating Tfh and Tfr cells were examined to identify specific immune responses in paediatric and adult individuals who recovered from asymptomatic to mild SARS-CoV-2 infection. Circulating Tfh and Tfr cells were evaluated by flow cytometry. To evaluate specific anti-SARS-CoV-2 immune responses, anti-Spike RBD IgG antibodies were measured by an enzyme-linked fluorescent assay, anti-Spike neutralizing activity - by an in vitro cell-based assay, and IFN-γ T cell responses were evaluated via ELISpot assay. Age-specific differences in the profiles of the CXCR5CD4 T cells that distinguish them from CXCR5- counterparts were detected. An increased percentage of cTfr cells and decreased percentage of cTfh cells was observed in the paediatric group, which resulted in a decreased cTfh/cTfr ratio. Increased proportions of ICOS- and HLA-DR-expressing cTfh and cTfr cells were also observed, consistent with the high proportion of antibody-responders among children. In contrast, a greater percentage of adults than children exhibited IFN-γ-positive T cells in response to the four viral peptides. In adult responders, a good correlation was found between the presence of plasmablasts and the cTfh/cTfr ratio. Antibody neutralizing capacity did not differ between children and adults. Circulating Tfh and Tfr cells exhibit specific age-dependent differences, which may contribute to the immunologic background of the clinical symptoms of SARS-CoV-2 infection.
FcγRIIb deficiency inhibits tumor development by attenuating the immunosuppressive phenotype of MDSCs.
Chen W, Pan J, Ning X … +6 more , Li D, Shen T, Cai L, Wang S, Qian L, Zhu X
Immunol Lett · 2026 Aug · PMID 41974282 · Publisher ↗
Regulation of myeloid-derived suppressor cell (MDSC) programming is critical for controlling tumor growth and anti-tumor immune responses. The role of FcγRIIb in MDSC programming was examined. FcγRIIb deficiency was foun...
Regulation of myeloid-derived suppressor cell (MDSC) programming is critical for controlling tumor growth and anti-tumor immune responses. The role of FcγRIIb in MDSC programming was examined. FcγRIIb deficiency was found to promote MDSC differentiation and increase splenic MDSC accumulation in tumor-bearing mice. This deficiency also attenuated the immunosuppressive phenotype of both polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. Tumor growth in FcγRIIb mice was significantly lower than in wild-type (WT) mice. Adoptive transfer of FcγRIIb MDSC subsets following B16F10/3LL injection significantly delayed tumor growth compared with transfer of WT MDSC subsets. Activation of the NF-κB pathway was observed in FcγRIIb MDSCs, which was associated with the diminished immunosuppressive phenotype. In human MDSCs, FcγRIIb expression was associated with the progression of lung cancer. These findings demonstrate that FcγRIIb is crucial for the immunosuppressive phenotype of MDSCs and may serve as a potential therapeutic target for anti-tumor therapy.
Appearing where it matters: Ectopic Germinal centers in the respiratory Tract after influenza infection.
Gailleton R, Angeletti D
Immunol Lett · 2026 Aug · PMID 41932401 · Publisher ↗
Influenza A virus infects the host through the respiratory mucosa, yet most vaccines are designed to elicit immune responses in secondary lymphoid organs that are anatomically distant from the site of infection. While ef...
Influenza A virus infects the host through the respiratory mucosa, yet most vaccines are designed to elicit immune responses in secondary lymphoid organs that are anatomically distant from the site of infection. While efficient at generating systemic immunity, these strategies often provide limited protection at mucosal surfaces. Recent studies have shown that infection-driven inflammation can induce the formation of tertiary lymphoid structures (TLS) throughout the respiratory tract, both in lungs but also in nasal tissue. Within these structures, ectopic germinal centers (eGCs) arise directly at sites of viral replication, supporting local B-cell activation, somatic hypermutation, class-switch recombination, and the generation of memory and antibody-secreting cells. Although eGCs share key features with conventional germinal centers, they develop under distinct inflammatory and stromal conditions that may influence B-cell selection as well as immune output which should be taken into consideration for future mucosal vaccine strategies. In this review, we summarize current understanding of respiratory eGC formation and function during influenza infection in mice and humans. We compare ectopic and conventional germinal center reactions, but also the eGC in lungs vs nasal tissues, discuss the local cues that drive TLS formation and how eGCs contribute to B cell selection and differentiation. Finally, we discuss how these insights may inform future influenza vaccine strategies aimed at engaging respiratory TLS to enhance durable mucosal immunity.
Analysis of Tim-4 expression in ulcerative colitis and its association with inflammation-related immune infiltration.
Liu Y, Wang Y, Wang X … +4 more , Zhu L, Zhao C, Zhu J, Wang X
Immunol Lett · 2026 Aug · PMID 41916431 · Publisher ↗
PURPOSE: To investigate the role of T-cell immunoglobulin and mucin domain 4 (Tim-4) in ulcerative colitis (UC) and its association with inflammation-related immune cell infiltration. METHOD: We analyzed Tim-4 expression...
PURPOSE: To investigate the role of T-cell immunoglobulin and mucin domain 4 (Tim-4) in ulcerative colitis (UC) and its association with inflammation-related immune cell infiltration. METHOD: We analyzed Tim-4 expression in patients with UC using the GSE87466 dataset and validated these findings through qPCR, ELISA, and immunohistochemistry of intestinal mucosal tissues collected from patients with UC and healthy control subjects. To evaluate the inflammatory response, hematoxylin and eosin (HE) staining was performed to assess the extent of inflammatory cell infiltration into the intestinal mucosa. Additionally, CIBERSORT analysis was performed to explore the correlation between Tim-4 expression and immune cell infiltration in patients with UC. Flow cytometry was used to quantify the proportion of immunosuppressive cells, such as regulatory T cells (Tregs) and CD14+HLA-DR-/low myeloid-derived suppressor cells (MDSCs), in both UC and control groups. RESULTS: Tim-4 expression was significantly elevated in patients with UC. It positively correlated with increased inflammatory cell infiltration and cytokine levels, particularly IL-17. Tim-4 was also associated with pro-inflammatory immune cells and a reduction in immunosuppressive cells, such as Tregs and MDSCs. CONCLUSION: Our findings indicate that Tim-4 expression is elevated in UC and is associated with alterations in both proinflammatory and immunosuppressive immune cell populations. These correlations suggest that Tim-4 may participate in the inflammatory processes of UC, potentially influencing immune cell infiltration and immune regulation. However, further mechanistic studies are required to determine the causal relationship and clarify the precise role of Tim-4 in UC pathogenesis.
Roles of group 2 innate lymphoid cells in development of steroid-resistant severe asthma and their therapeutic targets.
Matsuda M, Shimora H, Sannomiya Y … +1 more , Nabe T
Immunol Lett · 2026 Aug · PMID 41916430 · Publisher ↗
Severe asthma is characterized by persistent type 2 inflammation and airway remodeling that remain refractory to intensive glucocorticoid therapy. Accumulating evidence indicates that group 2 innate lymphoid cells (ILC2s...
Severe asthma is characterized by persistent type 2 inflammation and airway remodeling that remain refractory to intensive glucocorticoid therapy. Accumulating evidence indicates that group 2 innate lymphoid cells (ILC2s) play a central role in disease persistence and therapeutic refractoriness. ILC2s are rapidly activated by epithelial-derived cytokines such as interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-7, and produce large amounts of IL-5 and IL-13, thereby promoting eosinophilic inflammation and airway hyperresponsiveness. In severe asthma, chronic exposure to these cytokines induces pathogenic changes in ILC2s, including sustained proliferative capacity, profibrotic activity, and acquisition of resistance to glucocorticoid-induced apoptosis. Mechanistically, cooperative activation of the JAK-STAT5-Bcl-xL and PI3K-Akt-mTORC1 pathways enhances anti-apoptotic signaling and impairs glucocorticoid receptor function, allowing ILC2s to persist despite steroid treatment. This review focuses on the pathogenic roles of ILC2s in severe asthma, with particular emphasis on the molecular mechanisms underlying glucocorticoid resistance, and discusses emerging therapeutic strategies targeting these pathways to overcome steroid-resistant severe asthma.
Influences of age and sex on allergic symptoms in food allergy model mice.
Morii H, Haraoka N, Seki S … +1 more , Sugimoto Y
Immunol Lett · 2026 Aug · PMID 41912069 · Publisher ↗
BACKGROND: There are few studies on age and sex differences in food allergies, and many aspects remain unclear. In this study, we investigated the influences of age and sex differences in a food allergy model. METHODS: M...
BACKGROND: There are few studies on age and sex differences in food allergies, and many aspects remain unclear. In this study, we investigated the influences of age and sex differences in a food allergy model. METHODS: Mice were sensitized with OVA. Mice were observed for scratching behavior, sneezing, and nasal rubbing induced by oral administration of OVA. In addition, histamine sensitivity was evaluated by administering histamine intradermally and nasally. Additionally, antigen-specific IgE antibodies were measured. RESULTS: Scratching behavior, sneezing and nasal rubbing in food allergy decreased with age in both male and female mice. Nasal rubbing behavior increased in male mice compared with female mice in young mice, but decreased with age in both male and female mice. Furthermore, sneezing and nasal rubbing responses were increased in male mice compared with female mice. On the other hand, the antigen-specific IgE antibody decreased with age in both male and female mice, but increased in male mice compared to female mice. Furthermore, histamine-induced rhinitis symptoms also decreased with age. CONCLUSIONS: In food allergy model, it was found that rhinitis symptoms and antigen-specific IgE antibody levels decreased with age. It was also found that histamine-induced rhinitis symptoms decreased with age. Additionally, food allergy symptoms were found to be increased in male compared to female at young age. On the other hand, it was revealed that there was almost no sex difference in the symptoms of food allergy in aged mice.
Genetic disruption of Pdcd-1 upstream enhancer boosts T cell function and antitumor responses.
Jerin C, Seo W, Nishikawa H
Immunol Lett · 2026 Aug · PMID 41905426 · Publisher ↗
Programmed cell death 1 (PD-1) is an inhibitory receptor that drives T cell exhaustion in tumors, limiting antitumor immunity. Current PD-1 blockade therapies have shown limited success. To uncover new strategies for mod...
Programmed cell death 1 (PD-1) is an inhibitory receptor that drives T cell exhaustion in tumors, limiting antitumor immunity. Current PD-1 blockade therapies have shown limited success. To uncover new strategies for modulating PD-1, we investigated an upstream enhancer (UpEnh) of the Pdcd-1 gene using a CRISPR-Cas9 knockout mouse model. Deletion of the UpEnh reduced PD-1 expression across various T cell subsets. In a tumor setting, this deletion lowered PD-1 levels on intratumoral exhausted CD8⁺, conventional CD4⁺, Treg, and γδ T cells. This resulted in improved CD8⁺ and γδ T cell function and promoted stronger antitumor immunity. Our findings establish UpEnh as a critical regulator of PD-1, presenting a potential therapeutic target.
Per2 deficiency exacerbates IL-17-driven psoriasiform dermatitis in a diurnal-dependent manner.
Zhang L, Liu X, Lin Y … +2 more , Li P, Xie X
Immunol Lett · 2026 Aug · PMID 41864430 · Publisher ↗
Circadian clock genes regulate immune cell homeostasis, yet their contribution to inflammatory skin disorders remains incompletely understood. Here, we investigated the role of Period2 (Per2), a core circadian repressor,...
Circadian clock genes regulate immune cell homeostasis, yet their contribution to inflammatory skin disorders remains incompletely understood. Here, we investigated the role of Period2 (Per2), a core circadian repressor, in shaping T cell-driven psoriasiform inflammation. Per2 and wild-type mice (WT) were subjected to imiquimod (IMQ) -induced psoriasiform dermatitis. Disease severity, cutaneous pathology, immune cell subsets, cytokines, melatonin, and circadian regulators were assessed at ZT2 and ZT14 to evaluate diurnal variations. Per2 deficiency exacerbated IMQ-induced psoriasiform dermatitis, with higher PASI scores, epidermal hyperplasia, and parakeratosis, most pronounced at ZT14. It was also associated with increased serum melatonin, expansion of splenic Th17 and γδT cells, and elevated IL-17A, IL-17F, and TNF-α in serum and lesional skin. Mechanistically, Per2 loss resulted in a nocturnal surge of NFIL3 and RORγt expression, which mirrored the elevation of IL-17A even in the absence of increased IL-23. These findings indicate that Per2 loss aggravates psoriatic inflammation in a diurnal-dependent manner by enhancing IL-17-dominated immune responses, potentially involving the derepression of the NFIL3/RORγt axis.
Baseline immune signatures are associated with prospective COVID-19 infection and clinical outcomes in healthcare workers: Evidence from a cohort study in Brazil.
de Gois ET, Miranda VHS, Jardim-Santos GP … +21 more , Schulte HL, Canellas-de-Castro ME, Sasaki LMP, Fernandes GM, Soares AASM, Espindola LS, Kurizky PS, Gomes CM, Costa-Rocha IA, Brito-de-Sousa JP, Campi-Azevedo AC, Peruhype-Magalhães V, Teixeira-Carvalho A, de Albuquerque CP, Diogo PHJ, Rodrigues do Amaral L, Pascoal-Xavier MA, Coelho-Dos-Reis JGA, da Mota LMH, Martins-Filho OA, Nóbrega OT
Immunol Lett · 2026 Aug · PMID 41839271 · Publisher ↗
The present study intended to characterize the profile of serum immune mediators in healthcare professionals at the pandemic onset, aiming to identify baseline immunological patterns associated with prospective COVID-19...
The present study intended to characterize the profile of serum immune mediators in healthcare professionals at the pandemic onset, aiming to identify baseline immunological patterns associated with prospective COVID-19 diagnosis. A total of 386 participants with negative COVID-19 diagnosis were enrolled in a 19-month follow-up observational study. Quantitative analysis of immune mediators (chemokines, pro-inflammatory & regulatory cytokines and growth factors) was carried out by high-throughput multiplex array. All participants were SARS-CoV-2-negative at baseline, and immune mediators were measured prior to any documented COVID-19 diagnosis. Participants were categorized according to prospective diagnosis of COVID-19 [COVID-19 (-) and COVID-19 (+)], time elapsed prior COVID-19 (+) diagnosis, disease outcome and age ranges. Data demonstrated that participants with prospective COVID-19 (+) diagnosis presented higher levels of immune mediators as compared to COVID-19 (-). The higher the baseline levels of immune mediators, the shorter the elapsed time prior COVID-19 (+) diagnosis. GM-CSF, IL-5, VEGF, IL-13, CCL11 and IL-10 presented higher increment magnitude in COVID-19 (+) over the COVID (-) counterpart. Signatures profiles further confirmed these findings. Symptomatic or severe disease outcomes, as well as persistent symptom duration were associated with distinct profiles of immune mediators. Networks with higher correlation numbers were observed in COVID-19 (+), particularly in short-time prior prospective diagnosis, symptomatic mild disease and with short symptom duration. Multivariate and decision tree analysis demonstrated that GM-CSF, CCL11, CXCL10 and TNF-α effectively distinguished COVID-19 (+) individuals and pointed out that G-CSF was consistently associated with severe disease and prolonged symptom duration. These findings demonstrate that baseline serum immune mediator profiles are associated with prospective COVID-19 diagnosis and clinical outcomes, as identified through non-linear modeling.
The transcriptomic immune profiling across the different ileal layers highlights the relevant role of neutrophils and the active involvement of healthy mucosa in human Crohn's Disease.
Nannini G, Giudici F, Fink D … +9 more , Scaringi S, Cei F, Bertorello S, Russo E, Fortuna L, Staderini F, Cianchi F, Niccolai E, Amedei A
Immunol Lett · 2026 Aug · PMID 41819157 · Publisher ↗
BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory disorder characterized by discontinuous and transmural inflammation of the gastrointestinal tract. While most studies have focused on mucosal immunity a...
BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory disorder characterized by discontinuous and transmural inflammation of the gastrointestinal tract. While most studies have focused on mucosal immunity and individual immune cell subsets, little is known about the coordinated immune activity across the different ileal layers. This study aimed to characterize and compare, for the first time, the transcriptomic and immune landscape of the mucosa, submucosa, and serosa in diseased and adjacent healthy ileal tissue from CD patients. METHODS: Matched healthy and damaged ileal samples from 17 CD patients were dissected into three layers. Expression of 579 immune-related genes was quantified using the NanoString nCounter® GX Human Immunology V2 kit. RESULTS: Distinct transcriptional profiles were found between diseased and healthy tissues across all layers, with the mucosa showing the most pronounced dysregulation. Damaged mucosa exhibited upregulation of innate immunity-related genes, while neutrophil-associated transcripts and chemokines predominated in the serosa. Interestingly, healthy ileal tissue mirrored, layer by layer, the same distribution of innate (neutrophils) and adaptive (T and B) immune cells as diseased areas. A vertical immune gradient from mucosa to serosa was identified in both tissue types. CONCLUSIONS: This study provides novel insights into the compartmentalized immune architecture of the ileum in CD. The findings highlight a potential role of healthy tissue and serosal neutrophils in CD pathogenesis and progression. Layer-resolved transcriptomic profiling could aid early diagnosis, reveal new biomarkers, and support the development of personalized therapeutic strategies targeting specific ileal compartments.
Functional spectrum of γδ T cells in perinatal infectious diseases.
Lorga I, Léon-Lara X, Ravens S
Immunol Lett · 2026 Aug · PMID 41812905 · Publisher ↗
γδ T cells represent one of the earliest T cell lineages to develop and persist as long-lived cells after birth. During gestation, distinct developmental waves generate γδ T cells with restricted TCR diversity and pre-se...
γδ T cells represent one of the earliest T cell lineages to develop and persist as long-lived cells after birth. During gestation, distinct developmental waves generate γδ T cells with restricted TCR diversity and pre-set effector functions to mediate immune homeostasis and protection in early life. This review summarizes current knowledge on γδ T cell development, their postnatal maturation, and functional roles in utero and after birth. It highlights their robust and diverse effector responses, including cytotoxicity, cytokine production, and immune regulation, and their contribution to pathogen defense and tissue homeostasis. Together, these perspectives emphasize the functional diversity and developmental imprinting of γδ T cells, underscoring their importance for early-life immune competence and protection in vulnerable neonates.
Nipah virus: An immunological wake-up call for global health systems.
Esmaeeli S
Immunol Lett · 2026 Aug · PMID 41802635 · Publisher ↗
Nipah virus (NiV) is a highly lethal zoonotic pathogen that continues to re-emerge, as highlighted by recent confirmed cases in India. Although available studies suggest that the virus can disrupt innate immune signaling...
Nipah virus (NiV) is a highly lethal zoonotic pathogen that continues to re-emerge, as highlighted by recent confirmed cases in India. Although available studies suggest that the virus can disrupt innate immune signaling and induce humoral and cellular immune responses, the immunopathogenesis of human infection remains insufficiently understood. The absence of clearly defined immune correlates of protection limits effective preparedness and leaves outbreak responses largely reactive. This article argues that the primary bottleneck in NiV preparedness lies not in surveillance capacity, but in the lack of immunological frameworks that enable proactive outbreak response.
Src-family kinase control of CAR signaling: the paradoxical and multifaceted role of LCK.
Simeoni L, Mougiakakos D, Fricke S
Immunol Lett · 2026 Aug · PMID 41786049 · Publisher ↗
Lymphocyte-specific protein tyrosine kinase (LCK) is central to early T-cell receptor (TCR) signaling and is tightly regulated by phosphorylation, protein-protein interactions, and spatial organization to control T-cell...
Lymphocyte-specific protein tyrosine kinase (LCK) is central to early T-cell receptor (TCR) signaling and is tightly regulated by phosphorylation, protein-protein interactions, and spatial organization to control T-cell activation and fate. Chimeric antigen receptors (CARs) co-opt core elements of the TCR signaling machinery, including LCK. Nevertheless, important mechanistic differences, which remain largely unexplored, exist in how LCK is recruited, activated, and restrained during CAR signaling relative to canonical TCR signaling. Accumulating evidence indicates that CAR architecture, particularly the nature and organization of costimulatory signaling domains, profoundly influences LCK activity, signal strength, tonic signaling, and downstream differentiation outcomes. Excessive or sustained LCK activity can drive metabolic stress and exhaustion, whereas limiting or fine-tuning LCK signaling improves CAR T-cell persistence and therapeutic efficacy. Here, we review the current understanding of LCK regulation in CAR signaling and highlight recent insights into pharmacologic and structural strategies to tune LCK activity. A deeper understanding of LCK regulation is essential for improving the efficacy and safety of CAR T cells and may help in the design of next-generation CARs.
Association of computed tomography densitometry with disease progression and spatial heterogeneity in rheumatoid arthritis-associated interstitial lung disease.
Guo Z, Zhang Y, Li G … +7 more , Han N, Jiang X, Ma J, Qin Y, Zhu D, Gu X, Jin L
Immunol Lett · 2026 Aug · PMID 41771446 · Publisher ↗
OBJECTIVES: This study aimed to assess the efficacy of quantitative computed tomography (qCT) in distinguishing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and monitoring its progression. METHODS:...
OBJECTIVES: This study aimed to assess the efficacy of quantitative computed tomography (qCT) in distinguishing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and monitoring its progression. METHODS: HRCT images of 138 RA-ILD patients (GAP, n = 90; GAP, n = 48) and 47 RA controls were retrospectively analyzed. The normal lung attenuation areas (NL%), the percentage of low attenuation areas (LAA%), and the percentage of high-attenuation areas (HAA%) were measured for each lung lobe. Correlations between qCT indices and pulmonary function tests were evaluated using Spearman's rank correlation. ROC curves tested the discriminative performance of qCT indices. Multivariable logistic regression assessed associations between qCT indices and RA-ILD. RESULTS: The NL% decreased, while the LAA% and HAA% increased in the early and moderate-to-advanced stages of ILD, respectively (p < 0.05). Multivariate regression identified HAA% as an independent risk factor for ILD staging (OR: 1.737, 95% CI: 1.182-2.551, p = 0.005). When combining NL%, LAA%, and HAA%, the AUCs for early diagnosis and progression monitoring were 0.760 and 0.773, respectively (p < 0.05). RA-ILD exhibited spatial heterogeneity, with the lower lobes being primarily affected. CONCLUSIONS: Quantitative parameters can effectively differentiate early-stage RA-ILD and monitor its progression. LAA% is significantly correlated with early diagnosis, whereas HAA% demonstrates higher specificity in later stages. Quantitative lung densitometry may prove to be a valuable tool for clinical decision-making.
Vitamin D ameliorates NETosis and Th17/Treg imbalance in experimental autoimmune thyroiditis.
Yang HY, Wu XZ, Liu YP … +4 more , Jiang GY, Qin YF, Liang XH, Luo ZJ
Immunol Lett · 2026 Aug · PMID 41771445 · Publisher ↗
BACKGROUND: Neutrophil extracellular traps (NETs) have been implicated in various autoimmune diseases; however, their role in Hashimoto's thyroiditis (HT) remains poorly understood. This study aimed to characterize NETs...
BACKGROUND: Neutrophil extracellular traps (NETs) have been implicated in various autoimmune diseases; however, their role in Hashimoto's thyroiditis (HT) remains poorly understood. This study aimed to characterize NETs formation, explore its association with thyroid dysfunction and adaptive immunity, and evaluate the therapeutic potential of vitamin D (VD) in experimental autoimmune thyroiditis (EAT). METHODS: EAT was induced in BALB/c mice via thyroglobulin immunization combined with excess iodine intake. The VD group received additional intraperitoneal calcitriol supplementation. Thyroid histopathology, MHC-II expression, thyroid antibodies (TGAb and TPOAb), plasma DNase-I and 1,25(OH)₂D₃ levels, NETs formation, and splenic T cell subsets (Th17, Treg, Th1, Th2) and cytokines were assessed. Parallel experiments were conducted using neutrophils isolated from HT patients. RESULTS: Neutrophils from both EAT mice and HT patients exhibited enhanced NETosis compared to controls. EAT mice showed lower levels of DNase-I, 1,25(OH)₂D₃, Treg, and Th1 cells, along with higher Th17 and Th2 cells, elevated Th17/Treg ratio, and heightened thyroid MHC-II expression. NETs levels positively correlated with Th17, Th2, and MHC-II expression, and negatively with Treg, Th1, 1,25(OH)₂D₃, and DNase-I. VD supplementation mitigated thyroiditis and TPOAb levels, suppressed NETs formation, and reduced the Th17/Treg ratio and IL-17 levels. CONCLUSIONS: NETs contribute to Th17 bias and MHC-II over-expression in HT, suggesting a role in shaping the adaptive immune response. Vitamin D restrains NETosis and restores T-cell homeostasis, highlighting its potential as an adjunctive therapy for HT.
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