Journal of Experimental Medicine最新文献_第9页

NF-κB subunits RelA and c-Rel selectively control CD4+ T cell function in multiple sclerosis and cancer. NF-κB 亚基 RelA 和 c-Rel 可选择性地控制多发性硬化症和癌症中 CD4+ T 细胞的功能。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-06-03 Epub Date: 2024-04-02 DOI: 10.1084/jem.20231348

Guilhem Lalle, Raphaëlle Lautraite, Khaled Bouherrou, Maud Plaschka, Aurora Pignata, Allison Voisin, Julie Twardowski, Marlène Perrin-Niquet, Pierre Stéphan, Sarah Durget, Laurie Tonon, Maude Ardin, Cyril Degletagne, Alain Viari, Laurence Belgarbi Dutron, Nathalie Davoust, Thomas S Postler, Jingyao Zhao, Christophe Caux, Julie Caramel, Stéphane Dalle, Philippe A Cassier, Ulf Klein, Marc Schmidt-Supprian, Roland Liblau, Sankar Ghosh, Yenkel Grinberg-Bleyer

{"title":"NF-κB subunits RelA and c-Rel selectively control CD4+ T cell function in multiple sclerosis and cancer.","authors":"Guilhem Lalle, Raphaëlle Lautraite, Khaled Bouherrou, Maud Plaschka, Aurora Pignata, Allison Voisin, Julie Twardowski, Marlène Perrin-Niquet, Pierre Stéphan, Sarah Durget, Laurie Tonon, Maude Ardin, Cyril Degletagne, Alain Viari, Laurence Belgarbi Dutron, Nathalie Davoust, Thomas S Postler, Jingyao Zhao, Christophe Caux, Julie Caramel, Stéphane Dalle, Philippe A Cassier, Ulf Klein, Marc Schmidt-Supprian, Roland Liblau, Sankar Ghosh, Yenkel Grinberg-Bleyer","doi":"10.1084/jem.20231348","DOIUrl":"10.1084/jem.20231348","url":null,"abstract":"The outcome of cancer and autoimmunity is often dictated by the effector functions of CD4+ conventional T cells (Tconv). Although activation of the NF-κB signaling pathway has long been implicated in Tconv biology, the cell-autonomous roles of the separate NF-κB transcription-factor subunits are unknown. Here, we dissected the contributions of the canonical NF-κB subunits RelA and c-Rel to Tconv function. RelA, rather than c-Rel, regulated Tconv activation and cytokine production at steady-state and was required for polarization toward the TH17 lineage in vitro. Accordingly, RelA-deficient mice were fully protected against neuroinflammation in a model of multiple sclerosis due to defective transition to a pathogenic TH17 gene-expression program. Conversely, Tconv-restricted ablation of c-Rel impaired their function in the microenvironment of transplanted tumors, resulting in enhanced cancer burden. Moreover, Tconv required c-Rel for the response to PD-1-blockade therapy. Our data reveal distinct roles for canonical NF-κB subunits in different disease contexts, paving the way for subunit-targeted immunotherapies.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10986815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335853","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

Correction: Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis. 更正：JAK1变异体的个体受综合征的影响，包括自身免疫、过敏、结肠炎和皮炎。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-06-03 Epub Date: 2024-05-06 DOI: 10.1084/jem.2023238704302024c

Michael E Horesh, Marta Martin-Fernandez, Conor Gruber, Sofija Buta, Tom Le Voyer, Eve Puzenat, Harry Lesmana, Yiming Wu, Ashley Richardson, David Stein, Stephanie Hodeib, Mariam Youssef, Jacob A Kurowski, Elizabeth Feuille, Luis A Pedroza, Ramsay L Fuleihan, Alexandria Haseley, Alain Hovnanian, Pierre Quartier, Jérémie Rosain, Georgina Davis, Daniel Mullan, O'Jay Stewart, Roosheel Patel, Angelica E Lee, Rebecca Rubinstein, Leyla Ewald, Nikhil Maheshwari, Virginia Rahming, Ivan K Chinn, James R Lupski, Jordan S Orange, Vanessa Sancho-Shimizu, Jean-Laurent Casanova, Noura S Abul-Husn, Yuval Itan, Joshua D Milner, Jacinta Bustamante, Dusan Bogunovic

引用次数: 0

Sounding the alarm in the lung with TL1A. 用 TL1A 敲响肺部的警钟。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-06-03 Epub Date: 2024-04-10 DOI: 10.1084/jem.20240389

Silvia Pires, Randy S Longman

引用次数: 0

Divergent local and systemic antitumor response in primary uveal melanomas. 原发性葡萄膜黑色素瘤的局部和全身抗肿瘤反应存在差异。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-06-03 Epub Date: 2024-04-02 DOI: 10.1084/jem.20232094

Francesca Lucibello, Ana I Lalanne, Anne-Laure Le Gac, Abdoulaye Soumare, Setareh Aflaki, Joanna Cyrta, Lea Dubreuil, Martin Mestdagh, Marion Salou, Alexandre Houy, Christina Ekwegbara, Camille Jamet, Sophie Gardrat, Anais Le Ven, Karine Bernardeau, Nathalie Cassoux, Alexandre Matet, Denis Malaise, Gaelle Pierron, Sophie Piperno-Neumann, Marc-Henri Stern, Manuel Rodrigues, Olivier Lantz

{"title":"Divergent local and systemic antitumor response in primary uveal melanomas.","authors":"Francesca Lucibello, Ana I Lalanne, Anne-Laure Le Gac, Abdoulaye Soumare, Setareh Aflaki, Joanna Cyrta, Lea Dubreuil, Martin Mestdagh, Marion Salou, Alexandre Houy, Christina Ekwegbara, Camille Jamet, Sophie Gardrat, Anais Le Ven, Karine Bernardeau, Nathalie Cassoux, Alexandre Matet, Denis Malaise, Gaelle Pierron, Sophie Piperno-Neumann, Marc-Henri Stern, Manuel Rodrigues, Olivier Lantz","doi":"10.1084/jem.20232094","DOIUrl":"10.1084/jem.20232094","url":null,"abstract":"Uveal melanoma (UM) is the most common cancer of the eye. The loss of chromosome 3 (M3) is associated with a high risk of metastases. M3 tumors are more infiltrated by T-lymphocytes than low-risk disomic-3 (D3) tumors, contrasting with other tumor types in which T cell infiltration correlates with better prognosis. Whether these T cells represent an antitumor response and how these T cells would be primed in the eye are both unknown. Herein, we characterized the T cells infiltrating primary UMs. CD8+ and Treg cells were more abundant in M3 than in D3 tumors. CD39+PD-1+CD8+ T cells were enriched in M3 tumors, suggesting specific responses to tumor antigen (Ag) as confirmed using HLA-A2:Melan-A tetramers. scRNAseq-VDJ analysis of T cells evidenced high numbers of proliferating CD39+PD1+CD8+ clonal expansions, suggesting in situ antitumor Ag responses. TCRseq and tumor-Ag tetramer staining characterized the recirculation pattern of the antitumor responses in M3 and D3 tumors. Thus, tumor-Ag responses occur in localized UMs, raising the question of the priming mechanisms in the absence of known lymphatic drainage.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10986814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335851","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

Correction: Treg-tissue cell interactions in repair and regeneration. 更正：修复和再生过程中 Treg 与组织细胞的相互作用。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-06-03 Epub Date: 2024-05-13 DOI: 10.1084/jem.2023124405032024c

Lucas F Loffredo, Thomas M Savage, Olivia R Ringham, Nicholas Arpaia

引用次数: 0

Irene Salinas: The joy of continuous growth and learning. 艾琳-萨利纳斯不断成长和学习的快乐

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-06-03 Epub Date: 2024-05-21 DOI: 10.1084/jem.20240813

Lucie Van Emmenis

引用次数: 0

Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis. 患有 JAK1 变异的个体会受到综合征的影响，包括自身免疫、过敏、结肠炎和皮炎。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-06-03 Epub Date: 2024-04-02 DOI: 10.1084/jem.20232387

Michael E Horesh, Marta Martin-Fernandez, Conor Gruber, Sofija Buta, Tom Le Voyer, Eve Puzenat, Harry Lesmana, Yiming Wu, Ashley Richardson, David Stein, Stephanie Hodeib, Mariam Youssef, Jacob A Kurowski, Elizabeth Feuille, Luis A Pedroza, Ramsay L Fuleihan, Alexandria Haseley, Alain Hovnanian, Pierre Quartier, Jérémie Rosain, Georgina Davis, Daniel Mullan, O'Jay Stewart, Roosheel Patel, Angelica E Lee, Rebecca Rubinstein, Leyla Ewald, Nikhil Maheshwari, Virginia Rahming, Ivan K Chinn, James R Lupski, Jordan S Orange, Vanessa Sancho-Shimizu, Jean-Laurent Casanova, Noura S Abul-Husn, Yuval Itan, Joshua D Milner, Jacinta Bustamante, Dusan Bogunovic

{"title":"Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis.","authors":"Michael E Horesh, Marta Martin-Fernandez, Conor Gruber, Sofija Buta, Tom Le Voyer, Eve Puzenat, Harry Lesmana, Yiming Wu, Ashley Richardson, David Stein, Stephanie Hodeib, Mariam Youssef, Jacob A Kurowski, Elizabeth Feuille, Luis A Pedroza, Ramsay L Fuleihan, Alexandria Haseley, Alain Hovnanian, Pierre Quartier, Jérémie Rosain, Georgina Davis, Daniel Mullan, O'Jay Stewart, Roosheel Patel, Angelica E Lee, Rebecca Rubinstein, Leyla Ewald, Nikhil Maheshwari, Virginia Rahming, Ivan K Chinn, James R Lupski, Jordan S Orange, Vanessa Sancho-Shimizu, Jean-Laurent Casanova, Noura S Abul-Husn, Yuval Itan, Joshua D Milner, Jacinta Bustamante, Dusan Bogunovic","doi":"10.1084/jem.20232387","DOIUrl":"10.1084/jem.20232387","url":null,"abstract":"Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, treatment of one affected patient with severe atopic dermatitis using the JAK1/JAK2-selective inhibitor, baricitinib, resulted in clinically significant improvement. These findings suggest that individually rare JAK1 GoF variants may underlie an emerging syndrome with more common presentations of autoimmune and inflammatory disease (JAACD syndrome). More broadly, individuals who present with such conditions may benefit from genetic testing for the presence of JAK1 GoF variants.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10986756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335852","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

TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation. TL1A 是一种上皮警报蛋白，它与 IL-33 相互配合，共同引发过敏性气道炎症。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-06-03 Epub Date: 2024-04-10 DOI: 10.1084/jem.20231236

Pauline Schmitt, Anais Duval, Mylène Camus, Emma Lefrançais, Stéphane Roga, Cécile Dedieu, Nathalie Ortega, Elisabeth Bellard, Emilie Mirey, Emmanuelle Mouton-Barbosa, Odile Burlet-Schiltz, Anne Gonzalez-de-Peredo, Corinne Cayrol, Jean-Philippe Girard

{"title":"TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation.","authors":"Pauline Schmitt, Anais Duval, Mylène Camus, Emma Lefrançais, Stéphane Roga, Cécile Dedieu, Nathalie Ortega, Elisabeth Bellard, Emilie Mirey, Emmanuelle Mouton-Barbosa, Odile Burlet-Schiltz, Anne Gonzalez-de-Peredo, Corinne Cayrol, Jean-Philippe Girard","doi":"10.1084/jem.20231236","DOIUrl":"https://doi.org/10.1084/jem.20231236","url":null,"abstract":"Epithelium-derived cytokines or alarmins, such as interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), are major players in type 2 immunity and asthma. Here, we demonstrate that TNF-like ligand 1A (TL1A) is an epithelial alarmin, constitutively expressed in alveolar epithelium at steady state in both mice and humans, which cooperates with IL-33 for early induction of IL-9high ILC2s during the initiation of allergic airway inflammation. Upon synergistic activation by IL-33 and TL1A, lung ILC2s acquire a transient IL-9highGATA3low \"ILC9\" phenotype and produce prodigious amounts of IL-9. A combination of large-scale proteomic analyses, lung intravital microscopy, and adoptive transfer of ILC9 cells revealed that high IL-9 expression distinguishes a multicytokine-producing state-of-activated ILC2s with an increased capacity to initiate IL-5-dependent allergic airway inflammation. Similar to IL-33 and TSLP, TL1A is expressed in airway basal cells in healthy and asthmatic human lungs. Together, these results indicate that TL1A is an epithelium-derived cytokine and an important cofactor of IL-33 in the airways.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":15.3,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11010340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855150","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 culture shift to support public involvement and engagement in research. 转变文化，支持公众参与研究。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-06-03 Epub Date: 2024-05-15 DOI: 10.1084/jem.20240268

Matthias Eberl, Sheena M Cruickshank

引用次数: 0

Human neutrophils drive skin autoinflammation by releasing interleukin (IL)-26. 人类中性粒细胞通过释放白细胞介素（IL）-26 推动皮肤自身炎症。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-05-06 Epub Date: 2024-03-06 DOI: 10.1084/jem.20231464

Alessia Baldo, Jeremy Di Domizio, Ahmad Yatim, Sophie Vandenberghe-Dürr, Raphael Jenelten, Anissa Fries, Lorenzo Grizzetti, François Kuonen, Carle Paul, Robert L Modlin, Curdin Conrad, Michel Gilliet

引用次数: 0