Immunology letters最新文献

{"title":"Space immunology: Unraveling immune system dysregulation in long-duration spaceflight and its implications for earth-based autoimmune and inflammatory diseases","authors":"Muhammad Umar , Muhammad Talha","doi":"10.1016/j.imlet.2025.107063","DOIUrl":"10.1016/j.imlet.2025.107063","url":null,"abstract":"","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107063"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “The role of IgA in gastrointestinal helminthiasis: A systematic review” [Immunology Letters (2022) 12-22, Volume: 249]","authors":"Anne C.S. Ramos , Luciana M. Oliveira , Yvanna L.D.C.O. Santos , Marlon C.S. Dantas , Cristiani I.B. Walker , Ana M.C. Faria , Lílian L. Bueno , Silvio S. Dolabella , Ricardo T. Fujiwara","doi":"10.1016/j.imlet.2025.107011","DOIUrl":"10.1016/j.imlet.2025.107011","url":null,"abstract":"","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107011"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mast cell activation signature as a potential biomarker in COVID-19","authors":"Yatsiri G. Meneses-Preza ,&nbsp;Rodolfo Soria-Castro ,&nbsp;Ángel R. Alfaro-Doblado ,&nbsp;Alejandro Hernández-Solis ,&nbsp;Pablo Álvarez-Maldonado ,&nbsp;Diana Gómez-Martín ,&nbsp;Jiram Torres-Ruiz ,&nbsp;José Francisco Muñoz-Valle ,&nbsp;Guillermina Muñoz-Ríos ,&nbsp;Cristian Oswaldo Hernández-Ramírez ,&nbsp;Azmavet M. Güemes-González ,&nbsp;Isabel Wong-Baeza ,&nbsp;José Luis Maravillas-Montero ,&nbsp;Sonia M. Pérez-Tapia ,&nbsp;Alma D. Chávez-Blanco ,&nbsp;Sergio Estrada-Parra ,&nbsp;Rommel Chacón-Salinas","doi":"10.1016/j.imlet.2025.107026","DOIUrl":"10.1016/j.imlet.2025.107026","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by the SARS-CoV-2 virus, represented a public health challenge due to the absence of effective treatments to combat the disease. Lethality associated with SARS-CoV-2 infection results from an exacerbated immune response that mediates clinical disease progression and compromises respiratory capacity and organ function. In the lungs, one of the cell lineages increased during COVID-19 are mast cells (MC), cells of innate immune response known for their ability to promote inflammation through the release of their pre-formed mediators or <em>de novo</em> synthesis. The role of MC-derived mediators during SARS-CoV-2 infection and their association with the development of severe COVID-19 have been poorly described. In a previous report, we demonstrated the predictive ability of carboxypeptidase A3 (CPA3) to determine COVID-19 severity. However, it is currently unclear whether the use of other mast cell-derived mediators could improve this predictive ability. To address this gap, we evaluated levels of total tryptase, CPA3, chymase, and prostaglandin D2 (PGD2) in serum from patients with non-severe and severe COVID-19 to develop a predictive model of severe COVID-19 outcomes. We demonstrate that the combined use of these mediators enhances their predictive ability for MC activation during SARS-CoV-2 infection and their involvement in severe forms of COVID-19. Based on these findings, a serum MC activation profile can be proposed as a promising biomarker for SARS-CoV-2 infection and may contribute to the development of targeted therapeutic strategies to improve patient outcomes.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107026"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of afatinib on intestinal and salivary IgA: Immune response alterations linked to gastrointestinal side effects","authors":"Ippei Uemura,&nbsp;Natsuko Takahashi-Suzuki,&nbsp;Takashi Satoh","doi":"10.1016/j.imlet.2025.107024","DOIUrl":"10.1016/j.imlet.2025.107024","url":null,"abstract":"<div><h3>Background</h3><div>Afatinib, an oral molecular-targeted anticancer agent, is effective but causes significant gastrointestinal side effects. These effects are associated with EGFR inhibition in intestinal cells and changes in the microbiota.</div></div><div><h3>Objective</h3><div>To investigate the effects of afatinib on intestinal mucosal immunity in rats, focusing on IgA levels in the intestine and saliva, and to understand the innate and acquired immune responses to these side effects.</div></div><div><h3>Methods</h3><div>Male Wistar rats received afatinib (5.2 mg/kg) daily for 24 h (Day 1) and for 2 weeks (Day 14). Gene expression in the intestine was analyzed using quantitative polymerase chain reaction. IgA levels in the intestine and saliva were measured using enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>Afatinib suppressed α-defensin 5 and pIgR in the jejunum and ileum, indicating reduced innate immunity. It increased IgA levels in the intestine and saliva, suggesting altered acquired immunity. Salivary IgA levels significantly correlated with intestinal IgA levels.</div></div><div><h3>Conclusions</h3><div>Afatinib affects gastrointestinal mucosal immunity, suppresses innate defense, and alters IgA production. Salivary IgA could serve as a marker for monitoring these effects, aiding cancer therapy management.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107024"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitor of differentiation-2 protein ameliorates complete Freund's adjuvant-induced arthritis and inhibits STAT3 phosphorylation in the synovium","authors":"Yang Haowen ,&nbsp;Yao Yuhan ,&nbsp;Liang Yuanyuan ,&nbsp;Ma Xibin ,&nbsp;Wang Yuxin ,&nbsp;Xu Lingyun ,&nbsp;Yan Dong ,&nbsp;Li Min ,&nbsp;Zhong Genshen ,&nbsp;Wu Minna","doi":"10.1016/j.imlet.2025.107008","DOIUrl":"10.1016/j.imlet.2025.107008","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint inflammation, dysfunction, and deformity, along with systemic inflammatory manifestations. Inhibitor of differentiation-2 (ID2) is a transcription factor containing a helix-loop-helix (HLH) structure. Studies suggest that ID2 regulates innate and adaptive immunity and inhibits the differentiation of osteoclasts. However, the effects and underlying molecular mechanisms of ID2 on rheumatoid arthritis (RA) remain unclear. In the present study, we found that exogenous supplementation of human recombinant ID2 (hID2) protein significantly reduced paw swelling and arthritis index scores in adjuvant-induced arthritis (AIA) rats, and improved ankle joint pathology. Analysis of pro-inflammatory factor levels in peripheral blood mononuclear cells and synovial tissues indicated that hID2 attenuated inflammatory responses in AIA rats. Furthermore, RNA sequencing demonstrated that hID2 down-regulated the JAK-STAT pathway, and the phosphorylation of its key molecule, Signal Transducer and Activator of Transcription 3 (STAT3), was inhibited in synovial tissues. Additionally, the expression of chemokine-related genes was noticeably down-regulated in synovial tissues, though further investigation is needed to understand the underlying mechanisms. Overall, these findings suggest that hID2 effectively attenuated the inflammatory response and joint destruction in AIA rats, highlighting the potential of hID2 as a therapeutic agent for the treatment of RA.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107008"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low IL-35 expression in CSF is associated with Neuro-Behcet Disease: Comparative analysis between parenchymal and Non-parenchymal NBD","authors":"Kamel Hamzaoui ,&nbsp;FayçalHaj Sassi ,&nbsp;Mariem Salhi ,&nbsp;Agnès Hamzaoui","doi":"10.1016/j.imlet.2025.107031","DOIUrl":"10.1016/j.imlet.2025.107031","url":null,"abstract":"<div><h3>Background</h3><div>IL-35 is a recently discovered immunoregulatory cytokine that inhibits inflammatory cytokines by suppressing their lineage-specific transcription factors. The objective of this study was to investigate the expression of IL-35 in the cerebrospinal fluid (CSF) of patients with Neuro-Behçet Disease (NBD). An immuno-comparative analysis was performed between parenchymal NBD (pNBD) and non-parenchymal NBD (npNBD).</div></div><div><h3>Methods</h3><div>We are investigating CSF IL-35 levels in 45 patients with (NBD), comprising 25 patients with pNBD and 20 with npNBD, compared to 27 patients with multiple sclerosis (MS) and 20 patients with non-inflammatory neurological diseases (NIND). We assessed the inflammatory cytokines (IL-1α, IL-18, IL-33, IL-36), Foxp3 and CD4⁺ CD25⁺ Foxp3⁺ regulatory Treg T cells (Tregs). The following methodologies were employed: flow cytometry, ELISA, and real-time polymerase chain reaction (RT-PCR). For RT-PCR analysis, we calculated relative gene expression in target genes using the comparative CT method with the equation 2^−ΔΔCt. We employed a receiver operating characteristic (ROC) curve to investigate the predictive value of IL-35 levels.</div></div><div><h3>Results</h3><div>Protein and relative mRNA expression of IL-35 were significantly decreased in NBD and MS patients compared to the NIND group. Significantly lower CSF IL-35 mRNA (<em>p</em> <em>= 0.0001</em>) and protein (<em>p</em> <em>= 0.0004</em>) were observed in patients with pNBD compared to npNBD. The study revealed that NBD patients exhibited low Treg counts, and a significant positive correlation was identified between Treg numbers and CSF IL-35 (<em>r</em> = 0.554, <em>p</em> <em>= 0.0001</em>). Negative associations were observed between Tregs and CRP (<em>r</em> =- 0.518; <em>p</em> <em>= 0.0001</em>) and ESR (<em>r</em> = -0.571; <em>p</em> <em>= 0.0001</em>) in NBD. Levels of the pro-inflammatory mediators were found to be elevated in contrast to a low Foxp3 level in NBD, which was more reduced in pNBD compared to npNBD. In vitro cultured memory T cells from pNBD patients stimulated with LPS showed high levels of IL-1α, IL-18, IL-33, IL-36 and low levels of Foxp3 and IL-35 measured in the culture medium. After the addition of recombinant human IL-35 (rhIL-35), Foxp3 and IL-35 were significantly increased and inflammatory cytokine levels were reduced. These results suggest that rhIL-35 may induce a regulatory effect on Foxp3 and IL-35.</div></div><div><h3>Conclusion</h3><div>These findings imply a critical reduction of IL-35 in pNBD patients. The combined protein and gene expression of the tested inflammatory cytokines suggest that there are distinct inflammatory mechanisms governing the central nervous system in pNBD. Further work is essential for the development of targeted interventions for the effective treatment of patients.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107031"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin improves macrophage immune regulatory functions to alleviate airway Th2 polarization","authors":"Yixuan Dong ,&nbsp;Le Liu ,&nbsp;Xiwen Zhang ,&nbsp;Haoyue Zheng ,&nbsp;Yu Liu ,&nbsp;Aizhi Zhang ,&nbsp;Lingzhi Xu ,&nbsp;Yuanyi Zhang ,&nbsp;Gui Yang ,&nbsp;Pingchang Yang","doi":"10.1016/j.imlet.2025.107030","DOIUrl":"10.1016/j.imlet.2025.107030","url":null,"abstract":"<div><h3>Background</h3><div>Th2 polarization is a central driver of allergic airway inflammation, yet the epigenetic mechanisms underlying its dysregulation remain poorly defined. Quercetin is a bioactive flavonoid with immunomodulatory properties. This study investigates whether quercetin alleviates Th2-driven pathology in allergic airway inflammation by targeting IL-10 promoter hypermethylation in airway M2 macrophages.</div></div><div><h3>Methods</h3><div>Using a murine model of house dust mite (Derf2)-induced allergic airway inflammation, we isolated airway M2 macrophages via flow cytometry and assessed their immunosuppressive capacity using CFSE-based T cell proliferation assays. Epigenetic regulation of <em>Il10</em> was analyzed by bisulfite sequencing and chromatin immunoprecipitation. Quercetin (intranasal) was administered daily for 7 days.</div></div><div><h3>Results</h3><div>Allergic mice exhibited impaired M2 cell-mediated T cell suppression (proliferation index: 85% vs. 34% in controls, P &lt; 0.01) and IL-10 deficiency in bronchoalveolar lavage fluid (8.5 pg/ml vs. 28.2 pg/ml, P &lt;0.001). Il10 promoter hypermethylation (72% vs. 35% methylation at CpG sites -200 to +100) and reduced KDM5A recruitment were observed in M2 cells from allergic mice. Quercetin treatment reversed these epigenetic defects, restoring KDM5A binding (P &lt; 0.05) and Il10 transcription (2.1-fold increase, P &lt; 0.01), thereby reducing Th2 cytokines and airway hyperresponsiveness.</div></div><div><h3>Conclusions</h3><div>Our findings identify KDM5A-mediated <em>Il10</em> promoter demethylation as a critical mechanism for M2 cell immunoregulation in allergic airway inflammation. Quercetin alleviates Th2-driven pathology by restoring Il10 expression via epigenetic reprogramming of M2 macrophages. This study advances the understanding of natural compounds in targeting epigenetic checkpoints and provides a rationale for quercetin-based therapies in allergic diseases.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107030"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BENTA disease or CARD11 gain-of-function? A novel variant with atypical features and a literature review","authors":"Letizia Baldini ,&nbsp;Bärbel Keller ,&nbsp;Lisa Dewitte ,&nbsp;Chiara Passarelli ,&nbsp;Monia Ginevrino ,&nbsp;Diana Carli ,&nbsp;Davide Montin ,&nbsp;Xavier Bossuyt ,&nbsp;Klaus Warnatz ,&nbsp;Francesco Licciardi","doi":"10.1016/j.imlet.2025.107005","DOIUrl":"10.1016/j.imlet.2025.107005","url":null,"abstract":"<div><h3>Introduction</h3><div>The CARD11 (Caspase Recruitment Domain Family Member 11) gene encodes a scaffold protein critical for NF-κB signaling, regulating B-cell differentiation and T-cell effector functions. Gain-of-function (GOF) mutations in CARD11 cause BENTA disease (B cell Expansion with NF-κB and T cell Anergy), an autosomal dominant disorder typically presenting with early-onset polyclonal B-cell lymphocytosis, splenomegaly, lymphadenopathy, and recurrent infections.</div></div><div><h3>Methods</h3><div>We describe three related patients harboring a novel CARD11-GOF mutation (D357E), presenting with a BENTA phenotype with atypical features, including high IgM levels and a normal B-cell count, with life-threatening HLH in one case. Additionally, we conducted a systematic literature review using PubMed and EMBASE to identify previously reported cases of CARD11 GOF mutations.</div></div><div><h3>Results</h3><div><em>In vitro</em> functional analysis demonstrated that the D357E variant activates the NF-κB signaling pathway in primary lymphocytes and in HEK293T cells transfected with mutant CARD11. Our literature review identified 13 studies describing 29 patients. Notably, HLH emerged as a common complication of CARD11 GOF mutations (18.8 %), while B-lymphocytosis –though frequent– was not universally present.</div></div><div><h3>Conclusion</h3><div>We identified a novel pathogenic CARD11 variant and described its atypical phenotype, further expanding the clinical spectrum of CARD11 GOF disorders. These findings underscore the need for increased awareness of HLH risk in patients with CARD11 GOF mutations.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107005"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immune-reinforcements of Lenvatinib plus anti-PD-1 and their rationale to unite with TACE for unresectable hepatocellular carcinoma treatment","authors":"Jiayun Jiang ,&nbsp;Hui Zhang ,&nbsp;Yanjiao Ou ,&nbsp;Jiejuan Lai ,&nbsp;Yulan Huang ,&nbsp;Wenyun Cai ,&nbsp;Chong Li ,&nbsp;Leida Zhang ,&nbsp;Yu Fu","doi":"10.1016/j.imlet.2025.107003","DOIUrl":"10.1016/j.imlet.2025.107003","url":null,"abstract":"<div><h3>Background</h3><div>Despite encouraging clinical benefits have gained by anti-PD-1 and Lenvatinib combination, in-depth characterizations about the mechanisms of action remain poorly characterized. Furthermore, although the combination of systemic anti-PD-1 or Lenvatinib treatment and locoregional transcatheter arterial chemoembolization (TACE) is widely carried out to treat unresectable HCC in clinical, the efficacies of different combination regimens are uncertain due to limited researches.</div></div><div><h3>Methods</h3><div>We firstly generated murine HCC models to validate the enhanced anti-tumor effects of anti-PD-1 and Lenvatinib combination therapy. Then single cell mass cytometry (CyTOF) was employed to phenotypically reveal their mechanisms of action. After that, we further compared the effectiveness of TACE plus Lenvatinib (i.e., TACE-Len) dual therapy with TACE, Lenvatinib plus anti-PD-1 (i.e., TACE-Len-PD-1) triple therapy as conversion therapy for unresectable HCC.</div></div><div><h3>Results</h3><div>Lenvatinib and anti-PD-1 combination could generate activated immune profiles not only by increasing systemic CD4⁺, CD8⁺ <em>T</em> cells and B cells proportions, but also by weakening the immune-tolerance functions derived from both immunosuppressive cells (i.e., MDSCs) and co-inhibitory mediators (i.e., PD-L1 and LAG-3). Meanwhile, our study also suggested that TACE-Len-PD-1 triple therapy could achieve better clinical responses with powerful immune profiles for unresectable HCC compared to TACE-Len dual therapy.</div></div><div><h3>Conclusions</h3><div>Our study provided a delicate immune landscape of anti-PD-1and Lenvatinib combination, and we also offered scientific evidences that TACE-Len-PD-1 triple therapy could fulfill better clinical benefits than TACE-Len dual therapy, which is anticipated to provide objective and effective evidences for clinical use.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107003"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4+ T-cell help delivery to monocyte-derived dendritic cells promotes effector differentiation of helper and cytotoxic T cells","authors":"Douwe M. T. Bosma ,&nbsp;Julia Busselaar ,&nbsp;Mo D. Staal ,&nbsp;Elselien Frijlink ,&nbsp;Matthias Mack ,&nbsp;Fiamma Salerno ,&nbsp;Jannie Borst","doi":"10.1016/j.imlet.2025.107022","DOIUrl":"10.1016/j.imlet.2025.107022","url":null,"abstract":"<div><div>Delivery of CD4⁺ T-cell help optimizes CD8⁺ T-cell effector and memory responses via CD40-mediated licensing of conventional dendritic cells (DCs). Using comparative vaccination settings that prime CD8⁺ T cells in presence or absence of CD4⁺ T-cell help, we observed that CD4⁺ T-cell activation promoted influx of monocytes into the vaccine-draining lymph nodes (dLNs), where they differentiated into monocyte-derived (Mo)DCs, as defined by the most recent standards. Abrogation of these responses by CCR2-targeted depletion indicated that monocyte-derived cells in the dLN promoted T-helper 1 (Th1) type effector differentiation of CD4⁺ T cells, as well as effector differentiation of CD8⁺ T cells. Monocyte-derived cells in dLNs upregulated CD40, CD80 and PD-L1 as a result of CD4⁺ T-cell help. The response of monocyte-derived cells to CD4⁺ T-cell help was independent of natural killer (NK) cells and proceeded via CD40 ligand (L)-CD40 interactions and IFNγ signaling. Our data argue for a scenario wherein activated CD4⁺ T cells in dLNs crosstalk via CD40L and IFNγ signals to monocytes, promoting their local differentiation into MoDCs. This event enhances formation of CD4⁺ Th1 and CD8⁺ cytotoxic effector T cell pool, most likely by virtue of their improved costimulatory status and cytokine production.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107022"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}