The ChAT-acetylcholine pathway promotes group 2 innate lymphoid cell responses and anti-helminth immunity.

TitleThe ChAT-acetylcholine pathway promotes group 2 innate lymphoid cell responses and anti-helminth immunity.
Publication TypeJournal Article
Year of Publication2021
AuthorsChu, C, Parkhurst, CN, Zhang, W, Zhou, L, Yano, H, Arifuzzaman, M, Artis, D
JournalSci Immunol
Volume6
Issue57
Date Published2021 Mar 05
ISSN2470-9468
Abstract

Group 2 innate lymphoid cells (ILC2s) reside in multiple tissues, including lymphoid organs and barrier surfaces, and secrete type 2 cytokines including interleukin-5 (IL-5), IL-9, and IL-13. These cells participate in multiple physiological processes including allergic inflammation, tissue repair, metabolic homeostasis, and host defense against helminth infections. Recent studies indicate that neurotransmitters and neuropeptides can play an important role in regulating ILC2 responses; however, the mechanisms that underlie these processes in vivo remain incompletely defined. Here, we identify that activated ILC2s up-regulate choline acetyltransferase (ChAT)-the enzyme responsible for the biosynthesis of acetylcholine (ACh)-after infection with the helminth parasite or treatment with alarmins or cytokines including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). ILC2s also express acetylcholine receptors (AChRs), and ACh administration promotes ILC2 cytokine production and elicits expulsion of helminth infection. In accordance with this, ChAT deficiency in ILC2s leads to defective ILC2 responses and impaired immunity against helminth infection. Together, these results reveal a previously unrecognized role of the ChAT-ACh pathway in promoting type 2 innate immunity to helminth infection.

DOI10.1126/sciimmunol.abe3218
Alternate JournalSci Immunol
PubMed ID33674322