β2-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses

Saya Moriyama, Jonathan R. Brestoff, Anne Laure Flamar, Jesper B. Moeller, Christoph S.N. Klose, Lucille C. Rankin, Naomi A. Yudanin, Laurel A. Monticelli, Gregory Garbès Putzel, Hans Reimer Rodewald, David Artis

Research output: Contribution to journalArticlepeer-review

176 Scopus citations

Abstract

The type 2 inflammatory response is induced by various environmental and infectious stimuli. Although recent studies identified group 2 innate lymphoid cells (ILC2s) as potent sources of type 2 cytokines, the molecular pathways controlling ILC2 responses are incompletely defined. Here we demonstrate that murine ILC2s express the β2-adrenergic receptor (β2AR) and colocalize with adrenergic neurons in the intestine. β2AR deficiency resulted in exaggerated ILC2 responses and type 2 inflammation in intestinal and lung tissues. Conversely, β2AR agonist treatment was associated with impaired ILC2 responses and reduced inflammation in vivo. Mechanistically, we demonstrate that the β2AR pathway is a cell-intrinsic negative regulator of ILC2 responses through inhibition of cell proliferation and effector function. Collectively, these data provide the first evidence of a neuronal-derived regulatory circuit that limits ILC2-dependent type 2 inflammation.

Original languageEnglish
Pages (from-to)1056-1061
Number of pages6
JournalScience
Volume359
Issue number6379
DOIs
StatePublished - Mar 2 2018

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