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Neuropeptide CGRP Limits Group 2 Innate Lymphoid Cell Responses and Constrains Type 2 Inflammation.

TitleNeuropeptide CGRP Limits Group 2 Innate Lymphoid Cell Responses and Constrains Type 2 Inflammation.
Publication TypeJournal Article
Year of Publication2019
AuthorsNagashima H, Mahlakõiv T, Shih H-Y, Davis FP, Meylan F, Huang Y, Harrison OJ, Yao C, Mikami Y, Urban JF, Caron KM, Belkaid Y, Kanno Y, Artis D, O'Shea JJ
JournalImmunity
Date Published2019 Jul 16
ISSN1097-4180
Abstract

Innate lymphocytes maintain tissue homeostasis at mucosal barriers, with group 2 innate lymphoid cells (ILC2s) producing type 2 cytokines and controlling helminth infection. While the molecular understanding of ILC2 responses has advanced, the complexity of microenvironmental factors impacting ILC2s is becoming increasingly apparent. Herein, we used single-cell analysis to explore the diversity of gene expression among lung lymphocytes during helminth infection. Following infection, we identified a subset of ILC2s that preferentially expressed Il5-encoding interleukin (IL)-5, together with Calca-encoding calcitonin gene-related peptide (CGRP) and its cognate receptor components. CGRP in concert with IL-33 and neuromedin U (NMU) supported IL-5 but constrained IL-13 expression and ILC2 proliferation. Without CGRP signaling, ILC2 responses and worm expulsion were enhanced. Collectively, these data point to CGRP as a context-dependent negative regulatory factor that shapes innate lymphocyte responses to alarmins and neuropeptides during type 2 innate immune responses.

DOI10.1016/j.immuni.2019.06.009
Alternate JournalImmunity
PubMed ID31353223
Grant ListU01 AI095608 / AI / NIAID NIH HHS / United States