Interleukin-33 Induces the Enzyme Tryptophan Hydroxylase 1 to Promote Inflammatory Group 2 Innate Lymphoid Cell-Mediated Immunity

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2020 Mar 12

PMID 32160524

Citations 53

Authors

Anne-Laure Flamar

Christoph S N Klose

Jesper B Moeller

Tanel Mahlakoiv

Nicholas J Bessman

Wen Zhang

Saya Moriyama

Vladislava Stokic-Trtica

Lucille C Rankin

Gregory Garbes Putzel

Hans-Reimer Rodewald

Zhengxiang He

Lili Chen

Sergio A Lira

Gerard Karsenty

David Artis

Affiliations

Soon will be listed here.

Abstract

Group 2 innate lymphoid cells (ILC2s) regulate immunity, inflammation, and tissue homeostasis. Two distinct subsets of ILC2s have been described: steady-state natural ILC2s and inflammatory ILC2s, which are elicited following helminth infection. However, how tissue-specific cues regulate these two subsets of ILC2s and their effector functions remains elusive. Here, we report that interleukin-33 (IL-33) promotes the generation of inflammatory ILC2s (ILC2) via induction of the enzyme tryptophan hydroxylase 1 (Tph1). Tph1 expression was upregulated in ILC2s upon activation with IL-33 or following helminth infection in an IL-33-dependent manner. Conditional deletion of Tph1 in lymphocytes resulted in selective impairment of ILC2 responses and increased susceptibility to helminth infection. Further, RNA sequencing analysis revealed altered gene expression in Tph1 deficient ILC2s including inducible T cell co-stimulator (Icos). Collectively, these data reveal a previously unrecognized function for IL-33, Tph1, and ICOS in promoting inflammatory ILC2 responses and type 2 immunity at mucosal barriers.

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