Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses

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 recepto...

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Main Authors: 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.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:English
Published: Elsevier BV 2020
Online Access:https://hdl.handle.net/1721.1/126749
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author 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.
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
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.
author_sort Wallrapp, Antonia
collection MIT
description 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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spelling mit-1721.1/1267492022-10-03T11:13:54Z 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. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT 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. 2020-08-24T15:39:21Z 2020-08-24T15:39:21Z 2019-10 2019-06 2020-08-20T17:49:13Z Article http://purl.org/eprint/type/JournalArticle 1074-7613 https://hdl.handle.net/1721.1/126749 Wallrapp, Antonia et al. "Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses." Immunity 51, 4 (October 2019): P709-723.e6 © 2019 Elsevier Inc en http://dx.doi.org/10.1016/j.immuni.2019.09.005 Immunity Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Prof. Regev via Courtney Crummett
spellingShingle 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.
Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses
title Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses
title_full Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses
title_fullStr Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses
title_full_unstemmed Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses
title_short Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses
title_sort calcitonin gene related peptide negatively regulates alarmin driven type 2 innate lymphoid cell responses
url https://hdl.handle.net/1721.1/126749
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