ImmunityPub Date : 2026-09-03DOI: 10.1016/j.immuni.2026.08.014
Jennifer A. Lo,Inbal Rachmin,Jessica L. Flesher,Xunwei Wu,Akinori Kawakami,Miroslav Hejna,Judith R. Boozer,Nhu Nguyen,Andrew D. King,Yawen Ji,Sharon Germana,Lajos V. Kemeny,Anita A.J. van der Sande,Jeffrey B. Cheng,Michal Lotem,Torrey R. Utne,Yao Zhan,Elisabeth M. Roider,Nisma Mujahid,Elizabeth H. Byrne,Shailbala Singh,Manoubia Saidani,Sabrina Martineau,Nathalie Holic,Christine Baldeschi,Cécile Martinat,Gordon J. Freeman,Nir Hacohen,Keith T. Flaherty,Genevieve M. Boland,Jun S. Song,Arlene H. Sharpe,Shadmehr Demehri,Cassian Yee,Jennifer Allouche,David E. Fisher
{"title":"UV irradiation drives lineage-specific MITF-mediated transcription of PD-L1 to confer immune tolerance to UV-mutated melanocytes","authors":"Jennifer A. Lo,Inbal Rachmin,Jessica L. Flesher,Xunwei Wu,Akinori Kawakami,Miroslav Hejna,Judith R. Boozer,Nhu Nguyen,Andrew D. King,Yawen Ji,Sharon Germana,Lajos V. Kemeny,Anita A.J. van der Sande,Jeffrey B. Cheng,Michal Lotem,Torrey R. Utne,Yao Zhan,Elisabeth M. Roider,Nisma Mujahid,Elizabeth H. Byrne,Shailbala Singh,Manoubia Saidani,Sabrina Martineau,Nathalie Holic,Christine Baldeschi,Cécile Martinat,Gordon J. Freeman,Nir Hacohen,Keith T. Flaherty,Genevieve M. Boland,Jun S. Song,Arlene H. Sharpe,Shadmehr Demehri,Cassian Yee,Jennifer Allouche,David E. Fisher","doi":"10.1016/j.immuni.2026.08.014","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.08.014","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"57 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877411","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":"Long-lasting extracellular matrix modifications reshape intestinal stem cell fate and promote chronic inflammation","authors":"Idan Adir,Carmel Sochen,Sivan Gelb,Aviya Habshush Menachem,Sacha Lebon,Barak Toval,Vladyslav Holiar,Natalia Davidzohn,Tomer-Meir Salame,Irit Rosenhek-Goldian,Simonas Savickas,Fabio Sabino,Valerio Izzi,Bella Ungar,Alon Abend,Inna Solomonov,Ehud Zigmond,Taina Pihlajaniemi,Ulrich auf dem Keller,Moshe Biton,Irit Sagi","doi":"10.1016/j.immuni.2026.07.022","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.07.022","url":null,"abstract":"Tissue regeneration is viewed as a return to homeostasis, but whether the extracellular matrix (ECM) reverts during recovery from gut inflammation is unclear. Using temporal multi-omics, biomechanical profiling, and spatial fate mapping in colitis models, we showed that colonic ECM underwent lasting pathological reprogramming following inflammation, which we termed modified (mod)ECM. Characterized by collagen XVIII accumulation and immune-driven proteolysis, modECM redirected intestinal stem cells (ISCs) toward a wound-associated epithelial state with a pro-inflammatory transcriptional program. Ex vivo, modECM alone reshaped ISC fate by suppressing Wnt signaling and activating immune recruitment pathways. In vivo, modECM-rich zones sustained T cell infiltration and KRT14+ epithelial cell emergence from Lgr5+ progenitors. This aberrant epithelial program was mirrored in inflamed rectal biopsies from individuals with ulcerative colitis. Our findings redefine the ECM as a long-lived instructive compartment that encodes injury memory and promotes maladaptive regeneration, positioning it as a therapeutic target in chronic inflammatory diseases.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"159 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148821591","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}
ImmunityPub Date : 2026-08-26DOI: 10.1016/j.immuni.2026.07.023
Yixuan D. Zhou,Hailey Brown,Emily Schaffer,Gwen M. Taylor,Kay L. Fiske,Macy R. Komnick,Sebastian Lopez,Terence S. Dermody,Daria Esterházy
{"title":"T cell fate is dictated by different antigen-presenting cells in response to dietary versus gut epithelial self-antigen","authors":"Yixuan D. Zhou,Hailey Brown,Emily Schaffer,Gwen M. Taylor,Kay L. Fiske,Macy R. Komnick,Sebastian Lopez,Terence S. Dermody,Daria Esterházy","doi":"10.1016/j.immuni.2026.07.023","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.07.023","url":null,"abstract":"Mechanisms governing T cell responses to food or microbes have been characterized, but whether they also regulate gut autoimmunity is unknown. We compared ovalbumin (OVA)-specific T cell fates using mice fed OVA, or expressing secreted (s), cytosolic (c), or transmembrane (tm) epithelial OVA. At baseline and after reovirus infection, T cell responses were comparable. However, helminth infection induced T helper 2 (Th2) cell polarization in sOVA and tmOVA but not cOVA or OVA-fed mice. BATF3+ antigen-presenting cells (APCs) were indispensable for CD4+ T cell proliferation only in cOVA mice, yet they drove regulatory T (Treg) cell differentiation across all epithelial OVA models. In contrast, antigen presentation by RORγt+MHC class II+ APCs was exclusively required for Treg cell induction by dietary OVA. These distinct APC dependencies correlated with susceptibility to pathology elicited by dietary versus epithelial self-antigens. Thus, antigen origin and presentation context together shape T cell fate, aiding predictions of gut immune outcomes.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"3 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148821590","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}
ImmunityPub Date : 2026-08-24DOI: 10.1016/j.immuni.2026.08.001
Atishay Jay,Yeqiao Zhou,Sora Yoon,Bereketab N. Abeje,Aditi Chandra,Michael F. Michieletto,Julia Wald,Jorge Henao-Mejia,Arjun Raj,Robert B. Faryabi,Golnaz Vahedi
{"title":"Single-allele chromatin tracing reveals cytokine-dependent super-enhancer repositioning in CD4+ T cells","authors":"Atishay Jay,Yeqiao Zhou,Sora Yoon,Bereketab N. Abeje,Aditi Chandra,Michael F. Michieletto,Julia Wald,Jorge Henao-Mejia,Arjun Raj,Robert B. Faryabi,Golnaz Vahedi","doi":"10.1016/j.immuni.2026.08.001","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.08.001","url":null,"abstract":"Naive CD4+ T cells interpret cytokine cues to commit to T helper lineages. Here, we examined the impact of cytokines on the Ets1-Fli1 locus, which encodes paralogous transcription factors essential for T cell effector responses. Epigenomic and chromatin interaction profiling in double-positive (DP) thymocytes defined a T cell super-enhancer and a CTCF-bound boundary. Chromatin tracing at single-allele resolution revealed concurrent multi-way interactions among Ets1, Fli1, and the super-enhancer coupled to transcription. Deleting the CTCF boundary decompacted the locus without altering Ets1 expression or T cell development, whereas deleting the super-enhancer drew Ets1 and Fli1 closer; promoter proximity increased Ets1-Fli1 co-expression. In CD4+ Th1 cells, cytokines increased multi-way interactions and repositioned the super-enhancer toward the geometric center, activating both paralogs. Super-enhancer deletion rendered Th1 cells structurally and transcriptionally DP like. Thus, cytokines can drive lineage-specific gene activation by repositioning a super-enhancer, providing a mechanistic framework for how noncoding variants at the Ets1-Fli1 locus contribute to CD4+ T cell-mediated immune disorders.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"39 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805909","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":"An inflammatory bowel disease-linked lncRNA suppresses transcription factor T-BET expression in T cells to limit intestinal inflammation","authors":"Ruxiao Yang-Fischer,Alyssa Shearer,Jingyao Zhao,Theodore Nelson,Izortze Santin,Felipe Batista Leão,Ainara Castellanos-Rubio,Govind Bhagat,Uttiya Basu,Sankar Ghosh","doi":"10.1016/j.immuni.2026.07.019","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.07.019","url":null,"abstract":"Among the tens of thousands of annotated long noncoding RNAs (lncRNAs) in the human genome, only a small fraction have been functionally characterized. Here, we show that a well-established inflammatory bowel disease (IBD) risk locus encoded a conserved lncRNA, lnc15 (2310015A10Rik/ENSMUSG00000097729), whose structure was destabilized by risk-associated variants, leading to its degradation. Deletion of lnc15 in mice resulted in molecular features of inflammation under steady-state conditions and conferred heightened susceptibility to experimental colitis. Lnc15 was abundantly expressed in T cells, with highest expression in regulatory T (Treg) cells. Mechanistically, lnc15 suppressed the transcription factor T-BET by recruiting the CCR4-NOT RNA degradation complex to Tbx21 mRNA. Our study identifies that lnc15 simultaneously enhances Treg cell suppressive function and impairs conventional T cell pathogenicity in the context of intestinal inflammation. Collectively, these findings identify lnc15 as a functional lncRNA that links noncoding genetic variation to immune regulation and prevention of mucosal inflammation.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"19 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768892","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":"Metabolic inflammation, obesity, and cancer","authors":"Fawaz Alzaid,Camille Blériot,Gerasimos Anagnostopoulos,Svetoslav Chakarov,Nicolas Venteclef,Florent Ginhoux","doi":"10.1016/j.immuni.2026.07.020","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.07.020","url":null,"abstract":"Obesity is a global health concern, driving metabolic dysfunction and systemic inflammation. Here, we review the current understanding of the mechanisms underlying the impact of obesity in cancer susceptibility, progression, and response to therapy. We first discuss how resident and recruited macrophages adapt to metabolic stress within adipose tissue and the liver, which are metabolic hub tissues. We consider how obesity-driven myeloid reprogramming extends to other myeloid lineages and influences systemic immune function. Within this framework, where myeloid cells play conserved roles across tissues, we discuss cancer and how obesity-imprinted programs modify antitumor immunity irrespective of tumor site. We propose that local metabolic adaptation results in systemic immune consequences that impact tumor development and progression. Viewing cancer through the lens of obesity-related immunometabolic dysfunction may shed light on tissue- and cancer-specific responses and open avenues to improved therapies and management.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"37 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768893","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}
ImmunityPub Date : 2026-08-17DOI: 10.1016/j.immuni.2026.07.017
Vojo Deretic
{"title":"Canonical and noncanonical autophagy in immunity","authors":"Vojo Deretic","doi":"10.1016/j.immuni.2026.07.017","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.07.017","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"18 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148755372","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}
ImmunityPub Date : 2026-08-17DOI: 10.1016/j.immuni.2026.07.021
Zachary M. Earley, Anshul Rao, Longhui Qiu, Konrad Knöpper, Fanglue Peng, Norihide Jo, Ananya Krishnapura, Wioletta Lisicka, Hanna Taglinao, Jinping An, Ying Xu, Li V. Yang, Dan Liu, Mark R. Looney, Jason G. Cyster
{"title":"GPCR-Gα13 signaling regulates survival of intestinal intraepithelial CD8+ lymphocytes through migration to cytokine-rich niches","authors":"Zachary M. Earley, Anshul Rao, Longhui Qiu, Konrad Knöpper, Fanglue Peng, Norihide Jo, Ananya Krishnapura, Wioletta Lisicka, Hanna Taglinao, Jinping An, Ying Xu, Li V. Yang, Dan Liu, Mark R. Looney, Jason G. Cyster","doi":"10.1016/j.immuni.2026.07.021","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.07.021","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"12 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148755371","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}
ImmunityPub Date : 2026-08-14DOI: 10.1016/j.immuni.2026.08.006
Satish Devadas,Jyoti Das,Catherine Liu,Liying Zhang,Arthur I. Roberts,Zui Pan,Paul A. Moore,Gobardhan Das,Yufang Shi
{"title":"Granzyme B Is Critical for T Cell Receptor-Induced Cell Death of Type 2 Helper T Cells","authors":"Satish Devadas,Jyoti Das,Catherine Liu,Liying Zhang,Arthur I. Roberts,Zui Pan,Paul A. Moore,Gobardhan Das,Yufang Shi","doi":"10.1016/j.immuni.2026.08.006","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.08.006","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"49 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728042","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}
ImmunityPub Date : 2026-08-13DOI: 10.1016/j.immuni.2026.07.018
Jennifer A. Lo,Inbal Rachmin,Jessica L. Flesher,Xunwei Wu,Akinori Kawakami,Miroslav Hejna,Judith R. Boozer,Nhu Nguyen,Andrew D. King,Yawen Ji,Sharon Germana,Lajos V. Kemeny,Anita A.J. van der Sande,Jeffrey B. Cheng,Michal Lotem,Torrey R. Utne,Yao Zhan,Elisabeth M. Roider,Nisma Mujahid,Elizabeth H. Byrne,Shailbala Singh,Manoubia Saidani,Sabrina Martineau,Nathalie Holic,Christine Baldeschi,Cécile Martinat,Gordon J. Freeman,Nir Hacohen,Keith T. Flaherty,Genevieve M. Boland,Jun S. Song,Arlene H. Sharpe,Shadmehr Demehri,Cassian Yee,Jennifer Allouche,David E. Fisher
{"title":"UV irradiation drives lineage-specific MITF-mediated transcription of PD-L1 to confer immune tolerance to UV-mutated melanocytes","authors":"Jennifer A. Lo,Inbal Rachmin,Jessica L. Flesher,Xunwei Wu,Akinori Kawakami,Miroslav Hejna,Judith R. Boozer,Nhu Nguyen,Andrew D. King,Yawen Ji,Sharon Germana,Lajos V. Kemeny,Anita A.J. van der Sande,Jeffrey B. Cheng,Michal Lotem,Torrey R. Utne,Yao Zhan,Elisabeth M. Roider,Nisma Mujahid,Elizabeth H. Byrne,Shailbala Singh,Manoubia Saidani,Sabrina Martineau,Nathalie Holic,Christine Baldeschi,Cécile Martinat,Gordon J. Freeman,Nir Hacohen,Keith T. Flaherty,Genevieve M. Boland,Jun S. Song,Arlene H. Sharpe,Shadmehr Demehri,Cassian Yee,Jennifer Allouche,David E. Fisher","doi":"10.1016/j.immuni.2026.07.018","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.07.018","url":null,"abstract":"UV radiation (UVR) drives high mutational burdens, yet precursor melanocytes accumulate these mutations without triggering immune clearance. Here, we investigated whether melanocyte-intrinsic transcriptional program(s) underlie immune tolerance to mutations resulting from UVR exposure. In primary human melanocytes, expression of PD-L1 (CD274) was dependent on microphthalmia-associated transcription factor (MITF), a crucial regulator of melanocyte development and an intermediate in the UV-tanning pathway. MITF directly activated PD-L1 transcription by binding a conserved upstream enhancer containing functional E-box elements. MITF determined both baseline melanocytic PD-L1 expression in healthy skin and its induction following UVR, independent of interferon signaling. Melanocyte-restricted Pd-l1 deletion in mice triggered CD8+ T cell infiltration and depigmentation after long-term UVB exposure, recapitulating features of human vitiligo. PD-L1-deficient human induced pluripotent stem cell (iPSC)-derived melanocytes underwent increased apoptosis and were more susceptible than PD-L1-intact melanocytes to gp100-specific CD8+ T cell killing. Thus, a melanocyte-intrinsic MITF-PD-L1 tolerance program protects melanocytes from autoimmune destruction, potentially facilitating early immune evasion during melanoma development and conversely underlying the responsiveness of melanoma to PD-1/PD-L1 blockade.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"2 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148717824","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
