Journal of immunology最新文献

{"title":"CRISPR-Cas9 screen identifies eIF4G2 as a regulator of CD8+ T cell dysfunction.","authors":"Erin A Holcomb, Long Jiang, Ashley N Pearson, Jadyn James, Akshay Tate, Zhuwen Wang, Anwesha Dasgupta, Jim Clauwaert, Nicholas D Armas, Ameer L Elaimy, Dilrukshika S W Palagama, Samantha K Goodwin, Matthew J Kwiatkowski, Miguel Gijón, Meredith A Morgan, Adam H Courtney, Shannon A Carty, Amanda K Huber, Weiping Zou, John R Prensner, Michael D Green","doi":"10.1093/jimmun/vkag187","DOIUrl":"https://doi.org/10.1093/jimmun/vkag187","url":null,"abstract":"<p><p>CD8+ T cells directly target and kill cancer cells and are required for effective antitumor immunity. However, CD8+ T cells may become dysfunctional when exposed to chronic antigen stimulation during cancer. Dysfunction is characterized by reduced proliferation, increased expression of inhibitory receptors, and impaired effector function, yet the genetic mechanisms controlling dysfunction remain poorly understood. Therefore, we developed a murine ex vivo chronic stimulation model that recapitulates features of CD8+ T cell dysfunction observed within the tumor microenvironment. By coupling this system with genome-wide CRISPR-Cas9 loss-of-function screening, we discovered that the progression of murine CD8+ T cells to a dysfunctional state required eIF4G2, a noncanonical mRNA translation factor. Deletion of eIF4G2 restored CD8+ T cell survival and proliferation during chronic stimulation conditions in vitro. Transcriptomic, proteomic, and flow cytometric analyses revealed that eIF4G2 deletion shifts CD8+ T cell phenotype from a dysfunctional state to a proliferative state. eIF4G2 depletion reduced oxidative stress, lipid peroxidation, and accumulation of misfolded protein aggresomes during chronic in vitro stimulation. Finally, eIF4G2-depleted cells mediated enhanced tumor control in a murine model of melanoma. These data suggest that targeting eIF4G2 may promote CD8+ T cell resilience and improve therapeutic antitumor immunity.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient manganese exposure reprograms bone marrow-derived macrophages toward a stable anti-inflammatory memory state.","authors":"Yang Luo, Yu Cheng, Jia Zhang, Linying Li, Shih-Chin Cheng","doi":"10.1093/jimmun/vkag267","DOIUrl":"https://doi.org/10.1093/jimmun/vkag267","url":null,"abstract":"<p><p>Manganese ions (Mn2+) are potent immunomodulatory agents that activate the cGAS-STING pathway. While their role as acute adjuvants is well-documented, the innate immune memory (trained immunity) signatures induced by Mn2+ remain unexplored. Using an in vitro priming-rest-challenge model, we demonstrate that transient Mn2+ stimulation induces a persistent anti-inflammatory state in bone marrow-derived macrophages (BMDMs). Unlike the immediate proinflammatory burst associated with Mn2+, Mn2+-trained BMDMs displayed a stable reduction in Il6, Il1b, Il12a, and Nos2 expression upon secondary LPS or LPS + IFN-γ challenge. Furthermore, Mn2+ training enhanced IL-4-driven Arg1 induction and suppressed MHC class II surface expression, antigen presentation pathways, and phagocytic capacity against Candida albicans. Mechanistically, this functional attenuation was independent of glycolysis but correlated with a broad downregulation of lipid metabolic pathways. These findings reveal a lineage-specific regulatory \"brake\" induced by manganese, providing critical insights for its application in immunotherapy.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid-derived suppressor cells in hematologic malignancies: A current state of the field.","authors":"Yulia Nefedova, Dmitry I Gabrilovich","doi":"10.1093/jimmun/vkag249","DOIUrl":"10.1093/jimmun/vkag249","url":null,"abstract":"<p><p>Myeloid-derived suppressor cells are a pivotal component of the immunosuppressive tumor microenvironment in hematologic malignancies. Through diverse mechanisms, they promote disease progression, therapeutic resistance, and immune evasion. This comprehensive review synthesizes current evidence on the roles of myeloid-derived suppressor cells across major hematologic cancers and evaluates their prognostic significance, highlighting implications for patient stratification and potential therapeutic targeting.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and functional characterization of porcine T follicular helper and regulatory cells.","authors":"Daniel Zaki, Selma Schmidt, Joanna Wells, Persephone Borrow, Wilhelm Gerner, Simon P Graham, Jane C Edwards","doi":"10.1093/jimmun/vkag264","DOIUrl":"https://doi.org/10.1093/jimmun/vkag264","url":null,"abstract":"<p><p>T follicular helper (Tfh) cells provide help to B cells for antibody class switching and affinity maturation and are critical for germinal center (GC) formation. The frequency of Tfh cells has proven to be a valuable marker for predicting durable neutralizing antibody responses; conversely, the expansion of dysfunctional Tfh cells and increased T follicular regulatory (Tfr) cells are associated with suboptimal antibody responses. Given that the pig is becoming an appealing preclinical model for vaccine evaluation, a better understanding of porcine Tfh and Tfr cell populations is required. Novel reagents to detect CXCR5 and PD-1 were generated and deployed in a high-dimensional flow cytometry panel to identify putative Tfh and Tfr cells in porcine blood and lymphoid tissues. Higher frequencies of CXCR5+PD-1-BCL6-CD4+ and CXCR5hiPD-1+BCL6+CD4+ T cells, putative Tfh and GC Tfh cells, respectively, were detected in tonsils compared with other tissues, while higher frequencies of FoxP3+CXCR5+BCL6-CD4+ (putative Tfr) and FoxP3+CXCR5hiBCL6+CD4+ (putative GC Tfr) cells were present in the tracheobronchial lymph nodes. In an in vitro coculture model, both CXCR5hiPD-1+CD4+ and CXCR5+PD-1-CD4+ Tfh cells supported greater B cell proliferation, plasma cell formation, and antibody production than CXCR5-CD4+ T cells. A staining panel developed to profile cytokine and activation-induced marker expression revealed that following T cell receptor stimulation, CXCR5hiBCL6+CD4+ and CXCR5+BCL6-CD4+ cells expressed greater levels of CD40L, ICOS, and IL-4 than non-Tfh cells, resembling findings in human Tfh cells. These data lay the foundation for further studies on porcine Tfh and Tfr cells, and the exploration of strategies to harness these cells for improved vaccine-induced immunity.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ptpn1 deficiency collaborates with a NUP98::HOXD13 fusion gene to generate B cell precursor acute lymphoblastic leukemia.","authors":"Nupur Nigam, Toshihiro Matsukawa, Ryan Bertoli, Michel L Tremblay, Mianmian Yin, Yongmei Zhao, Yang Jo Chung, Peter D Aplan","doi":"10.1093/jimmun/vkag250","DOIUrl":"10.1093/jimmun/vkag250","url":null,"abstract":"<p><p>B cell precursor acute lymphoblastic leukemia (BCP ALL) is driven by a combination of genetic alterations that promote invasion and expansion of undifferentiated B cells. Mice that express a NUP98::HOXD13 (NHD13) fusion gene in hematopoietic cells develop a wide range of hematologic malignancy, and when crossed to mice that are prone to develop copy number aberrations (CNA), develop BCP ALL, accompanied by homozygous mutations of Ptpn1. To determine if Ptpn1 deletion can be a causal event leading to BCP-ALL, we crossed NHD13 mice with Ptpn1-/- mice. Mice with NHD13 expression and homozygous Ptpn1 loss developed BCP ALL with a penetrance of 70%, suggesting that Ptpn1 can function as a tumor suppressor gene in this context. Moreover, NHD13/Ptpn1+/- mice that developed BCP ALL typically showed a loss of the Ptpn1 wild type allele in leukemia cells, supporting the assertion that Ptpn1 can function as a tumor suppressor gene. Whole exome sequencing revealed acquired mutations in pathways typically mutated in human BCP ALL, such as B cell differentiation, signal transduction, and cytokine signaling. Transcriptomic analysis indicated -upregulation of signaling pathways in mitochondrial reprogramming and oxidative phosphorylation. In conclusion, we demonstrate the role of Ptpn1 as a tumor suppressor in controlling the development of B cell malignancies.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential requirements for cytokine signaling and local antigen in upper versus lower respiratory tract CD8+ TRM development.","authors":"Kirsten K Rodgers, Mark Elliott Williams, Ariana R Jimenez, Sakeenah L Hicks, Cameron L R Mattingly, Sarah E Michalets, Yixel M Soto-Vázquez, Kathryn M Moore, Madeleine M Rasche, Laurel A Lawrence, Yu-Shan Huang, Thien Duy Chen, Sofia R Cendoya, Christopher D Scharer, Alison Swaims-Kohlmeier, Jacob E Kohlmeier","doi":"10.1093/jimmun/vkag269","DOIUrl":"10.1093/jimmun/vkag269","url":null,"abstract":"<p><p>CD8+ tissue-resident memory T cells (TRM) in the upper respiratory tract (URT) limit viral replication after transmission and prevent spread to the lower respiratory tract (LRT), whereas LRT CD8+ TRM are important for limiting immunopathology in the lung and promoting efficient viral clearance. Although the presence of local respiratory antigen is thought to be required for CD8+ TRM development in the LRT but not the URT, the relationship between local antigen encounter and cytokine signaling that influences TRM differentiation in distinct niches of the respiratory tract remains unknown. Here, we show using murine models that while URT TRM generated in the presence or absence of local respiratory antigen are phenotypically, transcriptionally, and functionally similar throughout the respiratory tract, their developmental pathways are compartmentally distinct and characterized by a context-dependent compensatory relationship between antigen and cytokine signaling. In the absence of local antigen, URT CD8+ TRM formation required TGF-β signaling, and notably, while both IL-15 and IL-33 were broadly dispensable in the URT, IL-33 was able to rescue LRT CD8+ TRM development in the absence of local antigen. Together, these findings highlight key differences for CD8+ TRM development in distinct areas of the respiratory tract, offering valuable insights into the development of mucosal cellular immunity following intranasal and parenteral vaccination.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preservation of MHC-Ia protective allele suppression of SIVmac239 in aged rhesus macaques.","authors":"Alejandra Marenco, Benjamin Varco-Merth, Candice Nkoy, Aparna Govindan, Alvin Lam, He Li, Devin N Fachko, Derick Duell, William Goodwin, Omo Ogunwale, Margaret Terry, Rachel Dannay, Randy Fast, Kelli Oswald, Rebecca Shoemaker, Brandy Dozier, Anne D Lewis, Jeremy Smedley, Caralyn S Labriola, Michael Axthelm, Byung S Park, Jeffrey D Lifson, Louis J Picker, Rebecca L Skalsky, Scott W Wong, Afam A Okoye","doi":"10.1093/jimmun/vkag272","DOIUrl":"https://doi.org/10.1093/jimmun/vkag272","url":null,"abstract":"<p><p>Major histocompatibility complex class Ia (MHC-Ia)-restricted CD8⁺ T cell responses play a central role in the host defense against HIV-1, with certain MHC-Ia alleles known to be associated with cytotoxic T lymphocyte responses having an increased potential for viral control. However, the impact of immune aging on the effectiveness of such protective alleles remains unclear. In this study, we assessed SIVmac239 replication in aged (17-23 yr old) rhesus macaques (RMs) exhibiting low frequencies of naïve T cells and expanded effector memory T cells, that were further stratified by the presence (MHC⁺) or absence (MHC-) of 3 known \"protective MHC-Ia alleles\" (Mamu-A*01, Mamu-B*08, or Mamu-B*17). All RMs were infected with SIVmac239 and viral dynamics monitored longitudinally. MHC⁺ RMs demonstrated significantly lower plasma viral loads (PVLs) through 70 d postinfection compared with MHC- RMs. At 70 d postinfection, half of the RMs from each group initiated suppressive triple antiretroviral therapy comprising dolutegravir, emtricitabine, and tenofovir disoproxil fumarate (TDF) for 15 wk, followed by suboptimal TDF monotherapy for an additional 21 wk. While antiretroviral therapy substantially reduced PVL in both groups, viral decline was accelerated in MHC⁺ RMs relative to MHC- RMs. Moreover, upon switching to TDF monotherapy, PVL rebounded by almost 3 logs in MHC- RMs, while MHC⁺ RMs maintained viral suppression. Collectively, these findings indicate that protective MHC-Ia alleles can mediate viral control in aged hosts, even under suboptimal treatment conditions, and highlight the potential role of optimized CD8+ T cell responses in strategies targeting viral persistence in aging populations.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-Octyl itaconate suppresses IFN-γ-induced MHC II expression in bone marrow-derived macrophages.","authors":"Zhiying Zhou, Yixiu Ni, Shanshan Huang, Yijia Lin, Mingkun Yang, Yingwei Wu, Guolong Cai, Zhouxin Yang","doi":"10.1093/jimmun/vkag255","DOIUrl":"https://doi.org/10.1093/jimmun/vkag255","url":null,"abstract":"<p><p>Macrophages function as professional antigen-presenting cells that integrate inflammatory signals with metabolic reprogramming to shape immune responses. Itaconate, an immunometabolite derived from ACOD1/IRG1 activity in activated macrophages, has been implicated in the regulation of inflammatory responses, yet its role in interferon γ (IFN-γ)-driven antigen presentation programs remains incompletely understood. Here, we demonstrate that the itaconate derivative 4-octyl itaconate (4-OI) suppresses IFN-γ-induced antigen presentation programs in bone marrow-derived macrophages. 4-OI reduced surface major histocompatibility complex class II (MHC II) expression and downregulated key components of the antigen presentation machinery, including CIITA, H2-Ab1, and H2-Eb1. Transcriptomic analysis revealed broad suppression of IFN-γ-responsive immune pathways, particularly those associated with antigen processing and inflammatory signaling. Mechanistically, 4-OI attenuated IFN-γ-induced phosphorylation of JAK1, JAK2, and STAT1, and pharmacological inhibition of JAK signaling phenocopied its effects on MHC II expression, implicating involvement of the IFN-γ-JAK-STAT1-CIITA axis. In vivo, 4-OI similarly reduced IFN-γ-induced MHC II expression in splenic macrophages, accompanied by decreased PD-L1 expression as a parallel marker of macrophage activation. Together, these findings identify 4-OI as an immunometabolic regulator of IFN-γ-driven macrophage activation, associated with modulation of the JAK-STAT1-CIITA signaling axis and suppression of antigen presentation programs.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CTLA4 rs3087243-A-linked haplotype is associated with increased CTLA-4 expression and suppressive function in human regulatory T cells.","authors":"Lucas Nygård, Antti-Pekka Laine, Anna Jartti, Anna-Mari Schroderus, Viola Pitkänen, Laurène Pfajfer, Mikael Knip, Riitta Veijola, Jorma Ilonen, Jorma Toppari, Johanna Lempainen, Tuure Kinnunen","doi":"10.1093/jimmun/vkag276","DOIUrl":"https://doi.org/10.1093/jimmun/vkag276","url":null,"abstract":"<p><p>CTLA-4 is an inhibitory receptor on T cells that limits immune activation by competing with the co-stimulatory receptor CD28 for binding to CD80 and CD86 on antigen-presenting cells. Regulatory T cells (Tregs) employ CTLA-4-mediated transendocytosis as a key suppressive mechanism. Several CTLA4 polymorphisms are associated with autoimmune disease risk and may modulate CTLA-4 expression and function. Here, we analyzed samples from 155 genotyped subjects using flow cytometry and functional assays to determine how haplotypes formed by 3 CTLA4 single-nucleotide polymorphisms shape T-cell phenotype and function ex vivo. The autoimmune-protective CTLA4 rs5742909-rs231775-rs3087243 CAA haplotype was linked to increased intracellular CTLA-4 expression in both Tregs and conventional CD4+ T cells compared with CGG, CAG, and TAG haplotypes, implicating rs3087243 as the likely causal variant. The CAA haplotype was also associated with increased Treg frequencies. In Tregs from CAA/CAA subjects, elevated steady-state CTLA-4 expression promoted enhanced early CTLA-4 surface mobilization following anti-CD3/anti-CD28 stimulation. Moreover, naïve Tregs from CAA/CAA subjects more effectively suppressed naïve CD4+ T-cell proliferation in the presence of CD80/CD86-expressing dendritic cells. Collectively, these findings indicate that the rs3087243-A-linked CAA haplotype is associated with increased CTLA-4 expression and enhanced Treg function, providing a mechanistic explanation for its protective association with autoimmunity.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CTH522/CAF01 vaccination elicits clonally related Th17 subsets that mediate IL-17A-dependent protection against Chlamydia trachomatis.","authors":"Nina Dieu Nhien Tran Nguyen, Safia Guleed, Sharmila Subratheepam, Ernesto Marcos-Lopez, Matthieu Van Tilbeurgh, Marco Leonec, Anne-Sophie Galloüet, Katharina Wørzner, Joshua Woodworth, Thomas Lindenstrøm, Kristoffer Mazanti Melchiors, Tu Hu, Søren Hallstrøm, Roger Le Grand, Gabriel Kristian Pedersen, Rasmus Mortensen, Jan Pravsgaard Christensen, Frank Follmann, Jes Dietrich","doi":"10.1093/jimmun/vkag265","DOIUrl":"https://doi.org/10.1093/jimmun/vkag265","url":null,"abstract":"<p><p>Chlamydia trachomatis is the leading bacterial sexually transmitted pathogen worldwide and a major cause of reproductive tract disease, highlighting the need for an effective vaccine. Defining the immune mechanisms underlying vaccine-induced protection is therefore critical. We previously demonstrated that in mice vaccinated with CTH522/CAF01, genital tract Th17 cells correlated with protection against both infection and pathology. In this study, we further characterized these vaccine-induced Th17 cells in an infected genital tract. Fate-mapping and single-cell transcriptomic analyses revealed that CTH522/CAF01 vaccination generated multiple Th17-derived subsets, including a large memory-like population as well as effector Th17 and Th17-derived Th1-like subsets. These subsets shared common TCR clonotypes, and RNA velocity analyses predicted a unified differentiation trajectory, with one precursor population seeding both effector lineages. Our findings demonstrate a high degree of plasticity within the Th17 population and reveals previously uncharacterized Th17 subsets present during infection with C. trachomatis. Functional studies demonstrated that the Th17 subset that produced IL-17A was essential for early bacterial control, whereas IFN-γ-producing Th1 cells and Th17-derived Th1-like cells were not. Collectively, our findings provide mechanistic insight into Th17 biology and redefine the importance of IL-17A producing Th17 cells in early vaccine-mediated protection against C. trachomatis.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}