Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses
Name
Final submitted manuscript_Immunity 2019.pdf
Description
Accepted version
Size
29.93 MB
Format
Adobe PDF
Checksum (MD5)
5b7a0035c464a4a58f6f152d13bc8a47
Author(s)
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.
Date Issued
October 2019
Journal
Immunity
Publisher
Elsevier BV
Citation
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
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.immuni.2019.09.005
