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Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses.
Wallrapp, Antonia; Burkett, Patrick R; Riesenfeld, Samantha J; Kim, Se-Jin; Christian, Elena; Abdulnour, Raja-Elie E; Thakore, Pratiksha I; Schnell, Alexandra; Lambden, Conner; Herbst, Rebecca H; Khan, Pavana; Tsujikawa, Kazutake; Xavier, Ramnik J; Chiu, Isaac M; Levy, Bruce D; Regev, Aviv; Kuchroo, Vijay K.
Afiliação
  • Wallrapp A; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Burkett PR; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Riesenfeld SJ; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Kim SJ; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Christian E; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Abdulnour RE; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Thakore PI; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Schnell A; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Lambden C; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Herbst RH; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Khan P; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Tsujikawa K; Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan.
  • Xavier RJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Chiu IM; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
  • Levy BD; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Regev A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute and Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: aregev@broadinstitut
  • Kuchroo VK; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: vkuchroo@evergrande.hms.harvard.edu.
Immunity ; 51(4): 709-723.e6, 2019 10 15.
Article em En | MEDLINE | ID: mdl-31604686
Neuroimmune interactions have emerged as critical modulators of allergic inflammation, and type 2 innate lymphoid cells (ILC2s) are an important cell type for mediating these interactions. Here, we show that ILC2s expressed both the neuropeptide calcitonin gene-related peptide (CGRP) and its receptor. CGRP potently inhibited alarmin-driven type 2 cytokine production and proliferation by lung ILC2s both in vitro and in vivo. CGRP induced marked changes in ILC2 expression programs in vivo and in vitro, attenuating alarmin-driven proliferative and effector responses. A distinct subset of ILCs scored highly for a CGRP-specific gene signature after in vivo alarmin stimulation, suggesting CGRP regulated this response. Finally, we observed increased ILC2 proliferation and type 2 cytokine production as well as exaggerated responses to alarmins in mice lacking the CGRP receptor. Together, these data indicate that endogenous CGRP is a critical negative regulator of ILC2 responses in vivo.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neuropeptídeos / Linfócitos / Peptídeo Relacionado com Gene de Calcitonina / Receptores de Peptídeo Relacionado com o Gene de Calcitonina Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neuropeptídeos / Linfócitos / Peptídeo Relacionado com Gene de Calcitonina / Receptores de Peptídeo Relacionado com o Gene de Calcitonina Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article