Journal of Experimental Medicine最新文献_第10页

Th17-to-Tfh plasticity during periodontitis limits disease pathology. 牙周炎期间 Th17 到 Tfh 的可塑性限制了疾病的病理变化。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-05-31 DOI: 10.1084/jem.20232015

Flora A McClure, Kelly Wemyss, Joshua R Cox, Hayley M Bridgeman, Ian E Prise, James I King, Shafqat Jaigirdar, Annie Whelan, Gareth W Jones, John R Grainger, Matthew R Hepworth, Joanne E Konkel

{"title":"Th17-to-Tfh plasticity during periodontitis limits disease pathology.","authors":"Flora A McClure, Kelly Wemyss, Joshua R Cox, Hayley M Bridgeman, Ian E Prise, James I King, Shafqat Jaigirdar, Annie Whelan, Gareth W Jones, John R Grainger, Matthew R Hepworth, Joanne E Konkel","doi":"10.1084/jem.20232015","DOIUrl":"10.1084/jem.20232015","url":null,"abstract":"Th17 cell plasticity is crucial for development of autoinflammatory disease pathology. Periodontitis is a prevalent inflammatory disease where Th17 cells mediate key pathological roles, yet whether they exhibit any functional plasticity remains unexplored. We found that during periodontitis, gingival IL-17 fate-mapped T cells still predominantly produce IL-17A, with little diversification of cytokine production. However, plasticity of IL-17 fate-mapped cells did occur during periodontitis, but in the gingiva draining lymph node. Here, some Th17 cells acquired features of Tfh cells, a functional plasticity that was dependent on IL-6. Notably, Th17-to-Tfh diversification was important to limit periodontitis pathology. Preventing Th17-to-Tfh plasticity resulted in elevated periodontal bone loss that was not simply due to increased proportions of conventional Th17 cells. Instead, loss of Th17-to-Tfh cells resulted in reduced IgG levels within the oral cavity and a failure to restrict the biomass of the oral commensal community. Thus, our data identify a novel protective function for a subset of otherwise pathogenic Th17 cells during periodontitis.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 8","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179760","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}

引用次数: 0

Ki67 deficiency impedes chromatin accessibility and BCR gene rearrangement. Ki67 缺乏会阻碍染色质可及性和 BCR 基因重排。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-06 DOI: 10.1084/jem.20232160

Zhoujie Ding, Maree Hagan, Feng Yan, Nick W Y Schroer, Jack Polmear, Kim L Good-Jacobson, Alexandra R Dvorscek, Catherine Pitt, Kristy O'Donnell, Stephen L Nutt, Dimitra Zotos, Craig McKenzie, Danika L Hill, Marcus J Robinson, Isaak Quast, Frank Koentgen, David M Tarlinton

{"title":"Ki67 deficiency impedes chromatin accessibility and BCR gene rearrangement.","authors":"Zhoujie Ding, Maree Hagan, Feng Yan, Nick W Y Schroer, Jack Polmear, Kim L Good-Jacobson, Alexandra R Dvorscek, Catherine Pitt, Kristy O'Donnell, Stephen L Nutt, Dimitra Zotos, Craig McKenzie, Danika L Hill, Marcus J Robinson, Isaak Quast, Frank Koentgen, David M Tarlinton","doi":"10.1084/jem.20232160","DOIUrl":"10.1084/jem.20232160","url":null,"abstract":"The proliferation marker Ki67 has been attributed critical functions in maintaining mitotic chromosome morphology and heterochromatin organization during the cell cycle, indicating a potential role in developmental processes requiring rigid cell-cycle control. Here, we discovered that despite normal fecundity and organogenesis, germline deficiency in Ki67 resulted in substantial defects specifically in peripheral B and T lymphocytes. This was not due to impaired cell proliferation but rather to early lymphopoiesis at specific stages where antigen-receptor gene rearrangements occurred. We identified that Ki67 was required for normal global chromatin accessibility involving regulatory regions of genes critical for checkpoint stages in B cell lymphopoiesis. In line with this, mRNA expression of Rag1 was diminished and gene rearrangement was less efficient in the absence of Ki67. Transgenes encoding productively rearranged immunoglobulin heavy and light chains complemented Ki67 deficiency, completely rescuing early B cell development. Collectively, these results identify a unique contribution from Ki67 to somatic antigen-receptor gene rearrangement during lymphopoiesis.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 8","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261843","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}

引用次数: 0

Urine scRNAseq reveals new insights into the bladder tumor immune microenvironment. 尿液 scRNAseq 揭示了膀胱肿瘤免疫微环境的新见解。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-07 DOI: 10.1084/jem.20240045

Michelle A Tran, Dina Youssef, Sanjana Shroff, Disha Chowhan, Kristin G Beaumont, Robert Sebra, Reza Mehrazin, Peter Wiklund, Jenny J Lin, Amir Horowitz, Adam M Farkas, Matthew D Galsky, John P Sfakianos, Nina Bhardwaj

{"title":"Urine scRNAseq reveals new insights into the bladder tumor immune microenvironment.","authors":"Michelle A Tran, Dina Youssef, Sanjana Shroff, Disha Chowhan, Kristin G Beaumont, Robert Sebra, Reza Mehrazin, Peter Wiklund, Jenny J Lin, Amir Horowitz, Adam M Farkas, Matthew D Galsky, John P Sfakianos, Nina Bhardwaj","doi":"10.1084/jem.20240045","DOIUrl":"10.1084/jem.20240045","url":null,"abstract":"Due to bladder tumors' contact with urine, urine-derived cells (UDCs) may serve as a surrogate for monitoring the tumor microenvironment (TME) in bladder cancer (BC). However, the composition of UDCs and the extent to which they mirror the tumor remain poorly characterized. We generated the first single-cell RNA-sequencing of BC patient UDCs with matched tumor and peripheral blood mononuclear cells (PBMC). BC urine was more cellular than healthy donor (HD) urine, containing multiple immune populations including myeloid cells, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) in addition to tumor and stromal cells. Immune UDCs were transcriptionally more similar to tumor than blood. UDCs encompassed cytotoxic and activated CD4+ T cells, exhausted and tissue-resident memory CD8+ T cells, macrophages, germinal-center-like B cells, tissue-resident and adaptive NK cells, and regulatory DCs found in tumor but lacking or absent in blood. Our findings suggest BC UDCs may be surrogates for the TME and serve as therapeutic biomarkers.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 8","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283808","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}

引用次数: 0

Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus. 功能增益型人类 UNC93B1 变异可导致系统性红斑狼疮和瘃状狼疮。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-13 DOI: 10.1084/jem.20232066

Clémence David, Carlos A Arango-Franco, Mihaly Badonyi, Julien Fouchet, Gillian I Rice, Blaise Didry-Barca, Lucie Maisonneuve, Luis Seabra, Robin Kechiche, Cécile Masson, Aurélie Cobat, Laurent Abel, Estelle Talouarn, Vivien Béziat, Caroline Deswarte, Katie Livingstone, Carle Paul, Gulshan Malik, Alison Ross, Jane Adam, Jo Walsh, Sathish Kumar, Damien Bonnet, Christine Bodemer, Brigitte Bader-Meunier, Joseph A Marsh, Jean-Laurent Casanova, Yanick J Crow, Bénédicte Manoury, Marie-Louise Frémond, Jonathan Bohlen, Alice Lepelley

{"title":"Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus.","authors":"Clémence David, Carlos A Arango-Franco, Mihaly Badonyi, Julien Fouchet, Gillian I Rice, Blaise Didry-Barca, Lucie Maisonneuve, Luis Seabra, Robin Kechiche, Cécile Masson, Aurélie Cobat, Laurent Abel, Estelle Talouarn, Vivien Béziat, Caroline Deswarte, Katie Livingstone, Carle Paul, Gulshan Malik, Alison Ross, Jane Adam, Jo Walsh, Sathish Kumar, Damien Bonnet, Christine Bodemer, Brigitte Bader-Meunier, Joseph A Marsh, Jean-Laurent Casanova, Yanick J Crow, Bénédicte Manoury, Marie-Louise Frémond, Jonathan Bohlen, Alice Lepelley","doi":"10.1084/jem.20232066","DOIUrl":"10.1084/jem.20232066","url":null,"abstract":"UNC93B1 is a transmembrane domain protein mediating the signaling of endosomal Toll-like receptors (TLRs). We report five families harboring rare missense substitutions (I317M, G325C, L330R, R466S, and R525P) in UNC93B1 causing systemic lupus erythematosus (SLE) or chilblain lupus (CBL) as either autosomal dominant or autosomal recessive traits. As for a D34A mutation causing murine lupus, we recorded a gain of TLR7 and, to a lesser extent, TLR8 activity with the I317M (in vitro) and G325C (in vitro and ex vivo) variants in the context of SLE. Contrastingly, in three families segregating CBL, the L330R, R466S, and R525P variants were isomorphic with respect to TLR7 activity in vitro and, for R525P, ex vivo. Rather, these variants demonstrated a gain of TLR8 activity. We observed enhanced interaction of the G325C, L330R, and R466S variants with TLR8, but not the R525P substitution, indicating different disease mechanisms. Overall, these observations suggest that UNC93B1 mutations cause monogenic SLE or CBL due to differentially enhanced TLR7 and TLR8 signaling.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 8","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310776","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}

引用次数: 0

A human STAT3 gain-of-function variant drives local Th17 dysregulation and skin inflammation in mice. 人类 STAT3 功能增益变体会导致小鼠局部 Th17 失调和皮肤炎症。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-11 DOI: 10.1084/jem.20232091

Kelsey A Toth, Erica G Schmitt, Ana Kolicheski, Zev J Greenberg, Elizabeth Levendosky, Nermina Saucier, Kelsey Trammel, Vasileios Oikonomou, Michail S Lionakis, Eynav Klechevsky, Brian S Kim, Laura G Schuettpelz, Naresha Saligrama, Megan A Cooper

{"title":"A human STAT3 gain-of-function variant drives local Th17 dysregulation and skin inflammation in mice.","authors":"Kelsey A Toth, Erica G Schmitt, Ana Kolicheski, Zev J Greenberg, Elizabeth Levendosky, Nermina Saucier, Kelsey Trammel, Vasileios Oikonomou, Michail S Lionakis, Eynav Klechevsky, Brian S Kim, Laura G Schuettpelz, Naresha Saligrama, Megan A Cooper","doi":"10.1084/jem.20232091","DOIUrl":"10.1084/jem.20232091","url":null,"abstract":"Germline gain-of-function (GOF) variants in STAT3 cause an inborn error of immunity associated with early-onset poly-autoimmunity and immune dysregulation. To study tissue-specific immune dysregulation, we used a mouse model carrying a missense variant (p.G421R) that causes human disease. We observed spontaneous and imiquimod (IMQ)-induced skin inflammation associated with cell-intrinsic local Th17 responses in STAT3 GOF mice. CD4+ T cells were sufficient to drive skin inflammation and showed increased Il22 expression in expanded clones. Certain aspects of disease, including increased epidermal thickness, also required the presence of STAT3 GOF in epithelial cells. Treatment with a JAK inhibitor improved skin disease without affecting local Th17 recruitment and cytokine production. These findings collectively support the involvement of Th17 responses in the development of organ-specific immune dysregulation in STAT3 GOF and suggest that the presence of STAT3 GOF in tissues is important for disease and can be targeted with JAK inhibition.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 8","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300726","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}

引用次数: 0

Personalized cancer T-cell therapy takes the stage, mirroring vaccine success. 个性化癌症 T 细胞疗法登上舞台，反映了疫苗的成功。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-11 DOI: 10.1084/jem.20240854

Johanna Chiffelle, Alexandre Harari

引用次数: 0

Five decades of natural killer cell discovery. 发现自然杀伤细胞的五十年

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-06 DOI: 10.1084/jem.20231222

Lewis L Lanier

引用次数: 0

Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling. 柯萨奇病毒 A10 通过模拟 DKK1 来削弱 Wnt 信号，从而损害指甲再生并诱发甲沟炎。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-05 DOI: 10.1084/jem.20231512

Yingzi Cui, Qiaoni Shi, Pu Song, Jianyu Tong, Zhimin Cheng, Hangchuan Zhang, Xiaodan Wang, Yuxuan Zheng, Yao Wu, Meng Wan, Shihua Li, Xin Zhao, Zhou Tong, Zhengquan Yu, Shan Gao, Ye-Guang Chen, George Fu Gao

{"title":"Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.","authors":"Yingzi Cui, Qiaoni Shi, Pu Song, Jianyu Tong, Zhimin Cheng, Hangchuan Zhang, Xiaodan Wang, Yuxuan Zheng, Yao Wu, Meng Wan, Shihua Li, Xin Zhao, Zhou Tong, Zhengquan Yu, Shan Gao, Ye-Guang Chen, George Fu Gao","doi":"10.1084/jem.20231512","DOIUrl":"10.1084/jem.20231512","url":null,"abstract":"Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/β-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and β-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3β inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 8","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11153773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248186","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}

引用次数: 0

Maturation of germinal center B cells after influenza virus vaccination in humans. 人类接种流感病毒疫苗后生殖中心 B 细胞的成熟。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-27 DOI: 10.1084/jem.20240668

Katherine M McIntire, Hailong Meng, Ting-Hui Lin, Wooseob Kim, Nina E Moore, Julianna Han, Meagan McMahon, Meng Wang, Sameer Kumar Malladi, Bassem M Mohammed, Julian Q Zhou, Aaron J Schmitz, Kenneth B Hoehn, Juan Manuel Carreño, Temima Yellin, Teresa Suessen, William D Middleton, Sharlene A Teefey, Rachel M Presti, Florian Krammer, Jackson S Turner, Andrew B Ward, Ian A Wilson, Steven H Kleinstein, Ali H Ellebedy

{"title":"Maturation of germinal center B cells after influenza virus vaccination in humans.","authors":"Katherine M McIntire, Hailong Meng, Ting-Hui Lin, Wooseob Kim, Nina E Moore, Julianna Han, Meagan McMahon, Meng Wang, Sameer Kumar Malladi, Bassem M Mohammed, Julian Q Zhou, Aaron J Schmitz, Kenneth B Hoehn, Juan Manuel Carreño, Temima Yellin, Teresa Suessen, William D Middleton, Sharlene A Teefey, Rachel M Presti, Florian Krammer, Jackson S Turner, Andrew B Ward, Ian A Wilson, Steven H Kleinstein, Ali H Ellebedy","doi":"10.1084/jem.20240668","DOIUrl":"10.1084/jem.20240668","url":null,"abstract":"Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity and breadth to influenza hemagglutinin (HA) antigens compared with related GC clonotypes isolated earlier in the response. Structural studies of early and late GC-derived mAbs from one clonal lineage in complex with H1 and H5 HAs revealed an altered binding footprint. Our study shows that inducing sustained GC reactions after influenza vaccination in humans supports the maturation of responding B cells.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 8","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457369","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}

引用次数: 0

Human CD127 negative ILC2s show immunological memory. 人类 CD127 阴性 ILC2 显示出免疫记忆。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-18 DOI: 10.1084/jem.20231827

Laura Mathä, Lisette Krabbendam, Sergio Martinez Høyer, Balthasar A Heesters, Korneliusz Golebski, Chantal Kradolfer, Maryam Ghaedi, Junjie Ma, Ralph Stadhouders, Claus Bachert, Lars-Olaf Cardell, Nan Zhang, Gabriele Holtappels, Sietze Reitsma, Leanne Carijn Helgers, Teunis B H Geijtenbeek, Jonathan M Coquet, Fumio Takei, Hergen Spits, Itziar Martinez-Gonzalez

{"title":"Human CD127 negative ILC2s show immunological memory.","authors":"Laura Mathä, Lisette Krabbendam, Sergio Martinez Høyer, Balthasar A Heesters, Korneliusz Golebski, Chantal Kradolfer, Maryam Ghaedi, Junjie Ma, Ralph Stadhouders, Claus Bachert, Lars-Olaf Cardell, Nan Zhang, Gabriele Holtappels, Sietze Reitsma, Leanne Carijn Helgers, Teunis B H Geijtenbeek, Jonathan M Coquet, Fumio Takei, Hergen Spits, Itziar Martinez-Gonzalez","doi":"10.1084/jem.20231827","DOIUrl":"10.1084/jem.20231827","url":null,"abstract":"ILC2s are key players in type 2 immunity and contribute to maintaining homeostasis. ILC2s are also implicated in the development of type 2 inflammation-mediated chronic disorders like asthma. While memory ILC2s have been identified in mouse, it is unknown whether human ILC2s can acquire immunological memory. Here, we demonstrate the persistence of CD45RO, a marker previously linked to inflammatory ILC2s, in resting ILC2s that have undergone prior activation. A high proportion of these cells concurrently reduce the expression of the canonical ILC marker CD127 in a tissue-specific manner. Upon isolation and in vitro stimulation of CD127-CD45RO+ ILC2s, we observed an augmented ability to proliferate and produce cytokines. CD127-CD45RO+ ILC2s are found in both healthy and inflamed tissues and display a gene signature of cell activation. Similarly, mouse memory ILC2s show reduced expression of CD127. Our findings suggest that human ILC2s can acquire innate immune memory and warrant a revision of the current strategies to identify human ILC2s.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 8","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419414","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}

引用次数: 0