Immunity最新文献

{"title":"Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 signaling to establish T cell niches","authors":"Nagham Alouche, Hélène Cannelle, Stéphanie Favre, Marija Jokić, José A. Villegas, Sandra Maréchal, Clint De Nolf, Maeva Delacrétaz, Alexandros Sifis, Chloé Chapuis, Allison Burns, Giovanna Ambrosini, Isabelle Dupanloup, Jun Abe, Ute Koch, Nicolas Guex, Jens V. Stein, Ivan Maillard, Tom Cupedo, Burkhard Ludewig, Sanjiv A. Luther","doi":"10.1016/j.immuni.2026.03.023","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.03.023","url":null,"abstract":"Compartmentalization of secondary lymphoid organs is orchestrated by specialized fibroblastic reticular cells (FRCs), which guide immune cell migration, interaction, and function. Here, we investigated the pathways driving FRC differentiation into functionally distinct subsets. A Notch signaling signature distinguished lymph node (LN) FRCs, and deletion of <em>Notch1</em> and <em>Notch2</em> in FRCs restricted functional specialization, particularly for T-zone FRCs (T-zone reticular cells [TRCs]). Dendritic cell (DC)-specific deletion of the Notch ligand Jagged-1 prevented Ccl19^hi TRC differentiation, with homeostatic Ccr7⁺ DCs also being required for their maintenance. The resulting Ccl19 chemokine expression supported formation of central T-zone sub-compartments enriched in Xcr1⁺ DCs and CD8⁺ T cells. Both the spatial organization and Notch2-Jagged1 signaling activity were conserved in human LNs. Disrupting T-zone segregation via Notch2 inactivation in FRCs impaired the generation of CD8⁺ T cell memory precursors. Thus, Notch2-dependent TRC programming by DCs shapes distinct T-zone niches that sustain CD8⁺ T cell immunity.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"65 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAIT cells egress the thymus at several maturation stages with selective capacity to seed different tissues.","authors":"Rafael Almeida Paiva, Hugues Brière, Anne-Laure Le Gac, Aurélie Darbois, Laetitia Perrin, Anya Belmellat, Chaimae Saji, Mariela Furstenheim, Lea Guyonnet, François Legoux, Bernard Malissen, Marion Salou, Olivier Lantz","doi":"10.1016/j.immuni.2026.03.024","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.03.024","url":null,"abstract":"<p><p>Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) cells participate in tissue homeostasis and repair and in defense against pathogens. While MAIT and iNKT cells share a developmental pathway leading to the expression of effector-memory and tissue-residency programs, differences in subset proportions and tissue distribution suggest lineage-specific developmental mechanisms. We show that thymic epithelial cells contribute to MAIT but not to iNKT cell selection, which relies solely on double-positive thymocytes. Nonetheless, MAIT and iNKT cells had similar developmental kinetics and thymic residency properties. MAIT cells egressed the thymus at several developmental stages and colonized specific tissues. Semi-mature cells seeded the intestine via chemokine receptor CCR9. Thymic output during adulthood contributed to tissue MAIT and iNKT cell homeostasis. Lastly, MAIT ligands produced during colitis induced thymic MAIT17 cell expansion and migration to the colon, which suggests a feedback loop that boosts the production of MAIT cells capable of re-establishing epithelial integrity.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":""},"PeriodicalIF":26.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organ injury in systemic autoimmunity is mediated by stem-like CD8+ T cells arising from tissue-draining lymph nodes","authors":"Jafar Al Souz, Yulong Wei, Can Cui, Rihao Qu, Jin-Young Choi, Fang Wang, Steven J. Moioffer, Julia Barrett, Irene Chernova, Manvitha Nadella, Emily R. Siniscalco, Gilbert Moeckel, Nikhil S. Joshi, Ping-Min Chen, Arnon Arazi, The Accelerating Medicines Partnership: RA/SLE Network, Jennifer Anolik, William Apruzzese, Arnon Arazi, Jennifer Barnas, Michael Belmont, Celine Berthier, Michael B. Brenner, Jill Buyon, Phillip Carlucci, Robert Clancy, Sean Connery, Maria Dall’Era, Anne Davidson, Wade DeJager, Kristina Deonaraine, Betty Diamond, Patrick J. Dunn, Thomas Eisenhaure, Andrea Fava, Jennifer Goff, Beatrice Goilav, Jennifer Grossman, Joel Guthridge, Nir Hacohen, David Hildeman, Jeffery Hodgin, Paul Hoover, Raymond Hsu, Kazuyoshi Ishigaki, Mariko Ishimori, Peter Izmirly, Judith James, Tony Jones, Ken Kalunian, Diane L. Kamen, Ilya Korsunsky, Matthias Kretzler, Manjunath Kustagi, James Lederer, Jessica Li, David Lieb, Susan Macwana, Holden Maecker, Rong Mao, Maureen McMahon, Joseph Mears, Raji Menon, Nghia Millard, Pavel Morozov, Aparna Nathan, Fernanda Payan-Schober, Michael Peters, Michelle Petri, Chaim Putterman, Deepak A. Rao, Soumya Raychaudhuri, Bill Robinson, Saori Sakaue, Hemant Suryawanshi, Thomas Tuschl, P.J. Utz, Kathryn Weinand, Michael Weisman, David Wofsy, Steve Woodle, Qian Xiao, Fan Zhang, Ya-Chi Ho, Joseph Craft","doi":"10.1016/j.immuni.2026.03.022","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.03.022","url":null,"abstract":"Although loss of B cell tolerance, autoantibody production, and immune complex deposition are hallmarks of systemic lupus erythematosus (SLE), CD8<ce:sup loc=\"post\">+</ce:sup> T cell infiltration in the kidneys is the best predictor of poor prognosis in lupus nephritis, a severe manifestation of SLE. Here, we examined the origin, differentiation, and functional consequences of CD8<ce:sup loc=\"post\">+</ce:sup> T cells infiltrating kidneys in lupus-prone mice. TCF-1<ce:sup loc=\"post\">+</ce:sup> stem-like CD8<ce:sup loc=\"post\">+</ce:sup> T cells in renal-draining lymph nodes underwent T cell receptor (TCR)-dependent, antigen-driven expansion with differentiation into cytotoxic kidney-infiltrating cells that promoted tissue injury contingent on CD4<ce:sup loc=\"post\">+</ce:sup> T cell help and interleukin (IL)-21 and IL-15 signaling. CD8<ce:sup loc=\"post\">+</ce:sup> T cell differentiation was marked by persistent AP-1 activity and cytotoxic function despite increased expression of immune checkpoints. A parallel program of CD8<ce:sup loc=\"post\">+</ce:sup> T cell differentiation in the kidneys of patients with lupus nephritis reflected shared pathogenesis. Thus, a T cell differentiation program analogous to that in chronic infections and cancer is found in lupus; however, CD8<ce:sup loc=\"post\">+</ce:sup> T cells in systemic autoimmunity retain effector function despite terminal differentiation.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"17 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147736471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal dysbiosis exacerbates skin inflammation via microbial metabolite-driven Th2 cell differentiation","authors":"Lu Yu, Shuying Peng, Xi Chen, Tianxing Wu, Lijun Dong, Jialiang Luo, Shuangbin Xu, Jia Zhou, Xiaoshan Zhao, Lei Zheng, Gang Shu, Xuemin Wang, Liping Huang, Qingyun Chen, Deke Jiang, Liang-Dan Sun, Phillip Hylemon, Xiang-Yang Wang, Ledong Sun, Li Ma, Daming Zuo","doi":"10.1016/j.immuni.2026.03.019","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.03.019","url":null,"abstract":"The interplay between gut microbiota and the mucosal immune system critically regulates systemic immunity and disease susceptibility. Here, we demonstrate that intestinal epithelial Toll-like receptor (TLR)4 deficiency reshaped the gut microbiome and subsequently exacerbated atopic dermatitis (AD) in mice. Mechanistically, TLR4 deficiency reduced <em>Akkermansia muciniphila</em> abundance and enriched choline trimethylamine-lyase (CutC)-expressing bacteria. This enhanced microbial choline-to-trimethylamine conversion and elevated circulating trimethylamine oxide (TMAO) levels. Clinically, AD patients exhibited increased plasma TMAO levels that positively correlated with disease severity and immunoglobulin E (IgE) levels. UK Biobank data also showed that higher dietary choline intake was associated with increased AD risk. TMAO promoted T helper (Th)2 differentiation by directly interacting with protein phosphatase 5 (PPP5) and enhancing PPP5-mediated dephosphorylation of PPARγ. CD4⁺ T cell-specific PPARγ deletion abolished TMAO-driven skin pathology in AD mice. Our results reveal intestinal dysbiosis, as a result of innate immune deficiency, as a driver of inflammatory Th2 cells and AD pathology, highlighting a link among the gut immune environment, microbial metabolites, and skin disease.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"26 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin inflammation and itch response are independently regulated by distinct nociceptor subsets.","authors":"Tiphaine Voisin, Nadine Gheziel, Céline El Samrout, Jérémy Martin, Amyaouch Bradaia, Mircea Iftinca, Manon Defaye, Aude Charron, Nasser S Abdullah, Celia Changenot, Anne-Alicia Gonzalez, Antoine Depluech, Elodie Labit, Nathalie Saint-Laurent, Larissa Staurengo-Ferrari, Ozge Erdogan, Marie Tauber, Alexia Loste, Nadine Serhan, Sara Villa-Hernandez, Isaac M Chiu, Aziz Moqrich, Christophe Altier, Lilian Basso, Nicolas Gaudenzio","doi":"10.1016/j.immuni.2026.03.020","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.03.020","url":null,"abstract":"<p><p>Common dermatological disorders are characterized by inflammation and severe itching, which represent a significant clinical challenge. The mechanisms by which nociceptive sensory neurons (nociceptors) integrate peripheral signals to modulate inflammation and itch remain unclear. Here, we showed that two subsets of nociceptors had distinct and nonredundant biological functions in a model of allergic contact dermatitis (ACD). Retrograde axonal tracing of skin-projecting neurons combined with single-cell profiling identified a subset of MrgprD⁺ nonpeptidergic neurons that adopted a transitory regenerative program in response to skin inflammation. Selective ablation of reprogrammed MrgprD⁺ nonpeptidergic neurons during ACD-like inflammation abolished itch-evoked behavior but did not affect skin inflammation. Conversely, selective depletion of Trpv1⁺ peptidergic neurons exacerbated inflammation through increased neutrophilic infiltration without impacting itch-evoked behavior. This study reveals the presence of two distinct and adaptive neuronal circuits that independently regulate allergic inflammation and itch in the skin.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":""},"PeriodicalIF":26.3,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma cell ontogenies, functions, and lifespans","authors":"Colin A. Fields, Deepta Bhattacharya","doi":"10.1016/j.immuni.2026.01.030","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.01.030","url":null,"abstract":"B cell development is one of the best-understood processes within the immune system. Coordination between transcriptional programs and antigen receptor assembly determines B cell fate, diversifies the antibody repertoire, and allocates specificities to the best-suited subsets. This enables B cells to respond to a wide variety of challenges, which, when encountered, can lead B cells to seemingly converge upon a common fate: the antibody-secreting plasma cell. Yet, as we discuss in this review, this convergence is not complete. Developmental origins, anatomical sites, the nature of the challenge, and other factors all leave their marks on plasma cells in ways that diversify their functions and longevity. Looking forward, these marks may provide targets to engineer vaccines that provide durable antibody-mediated immunity.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"59 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147681506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two to tango: Microglia in glioblastoma invasion","authors":"Donn A. Van Deren, Malay Haldar","doi":"10.1016/j.immuni.2026.03.016","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.03.016","url":null,"abstract":"A lethal feature of glioblastoma is its ability to spread within the brain. In this issue of <ce:italic>Immunity</ce:italic>, Nebeling et al. use longitudinal three-photon imaging in an immunocompetent glioblastoma model to show that microglial responses at the far infiltration zone are spatially restricted and biphasic, with CX3CR1 signaling modulating tumor invasion dynamics.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"3 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147681505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage metabolic exhaustion and PANoptotic cell death drive chronic tissue inflammation in rheumatoid arthritis.","authors":"Tao Huang, Yoshinori Takashima, Jitendra Kumar, Jose Morales, Kevin Le, Zhensheng Hu, Selene Rubino, Robert T Trousdale, Gerald J Berry, Jorg J Goronzy, Cornelia M Weyand","doi":"10.1016/j.immuni.2026.01.019","DOIUrl":"10.1016/j.immuni.2026.01.019","url":null,"abstract":"<p><p>In the autoimmune disease rheumatoid arthritis, the inflammatory response evolves from protective to pathogenic, causing tissue destruction. Rheumatoid synovitis persists despite the presence of pro-repair SELENOP^hiMerTK⁺CD206⁺ macrophages, suggesting that these cells acquire pro-arthritogenic functions. Patient-derived synovial SELENOP^hiMerTK⁺CD206⁺ macrophages produced high concentrations of the complement component C1q and concurrently expressed its receptor, C1QBP. Stimulation of these macrophages with C1q induced metabolic exhaustion, characterized by diminished ATP production, cleavage of mitochondrial nicotinamide adenine dinucleotide (NAD), and accumulation of cyclic ADP ribose (cADPR). This metabolic crisis was driven by the mitochondrial enzyme Sterile alpha and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1), which catalyzed the conversion of NAD into cADPR, triggering PANoptotic and pro-inflammatory macrophage death. In vivo experiments demonstrated that C1q treatment exacerbated synovitis, whereas SARM1 inhibition conferred therapeutic benefit. These findings identify the NAD⁺ hydrolase SARM1 as a marker of metabolically stressed macrophages and an executor of pro-inflammatory macrophage death during autoimmune tissue inflammation.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"970-987.e6"},"PeriodicalIF":26.3,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A fast way to lose antibodies","authors":"Sheenam Verma, Oliver J. Harrison","doi":"10.1016/j.immuni.2026.03.018","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.03.018","url":null,"abstract":"Long-lived plasma cells maintain antibody titers that sustain humoral immunity, yet the physiological cues regulating their persistence remain incompletely understood. In this issue of <ce:italic>Immunity</ce:italic>, Zhu et al. reveal that fasting-induced β-hydroxybutyrate destabilizes bone marrow plasma cell niches through HCAR2 signaling, accelerating the loss of long-lived plasma cells and humoral immunity.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"12 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147681171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B lymphocytes that enter the germinal center late preferentially differentiate into memory cells that recognize subdominant epitopes.","authors":"Pengcheng Zhou, Harald Hartweger, Andrew J MacLean, Victor Ramos, Kai-Hui Yao, Brianna Hernandez, Zijun Wang, Anna Gazumyan, Michel C Nussenzweig","doi":"10.1016/j.immuni.2026.01.027","DOIUrl":"10.1016/j.immuni.2026.01.027","url":null,"abstract":"<p><p>Germinal center (GC) responses are initially seeded by founder B cells and subsequently diversified by continual entry of naive B cells that compete for antigen and T cell help. Here, we examined the contribution of these later-arriving invaders to the development of plasma cells (PCs) and memory B cells (MBCs). We developed a dual-recombinase reporter approach that enabled pre- and post-GC B cell lineage tracing upon vaccination or infection. After immunization with haptenated antigen, a combination tetanus and diphtheria vaccine (Tenivac), or SARS-CoV-2, fate-mapped invaders preferentially gave rise to MBCs as opposed to PCs. Antibodies expressed by invader-derived MBCs harbored fewer somatic mutations, exhibited lower affinity, and bound to subdominant antigenic epitopes relative to founder MBCs. Invader-derived MBCs also contributed to repertoire diversification after infection with murine-adapted influenza A. Our findings indicate that invader GC B cells are an important source of humoral immune memory diversification after vaccination or infection.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"1025-1038.e5"},"PeriodicalIF":26.3,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}