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

• Published in: Science (American Association for the Advancement of Science) Vol. 359; no. 6379; pp. 1056 - 1061
• Main Authors: Moriyama Saya, Brestoff, Jonathan R, Flamar Anne-Laure, Moeller, Jesper B, Klose Christoph S N, Rankin, Lucille C, Yudanin, Naomi A, Monticelli, Laurel A, Putzel Gregory Garbès, Hans-Reimer, Rodewald, Artis, David
• Format: Journal Article
• Language: English
• Published: Washington The American Association for the Advancement of Science 02.03.2018
• Subjects: Adrenergic receptors; Allergens; Anatomy; Cell proliferation; Cytokines; Down-regulation; Environmental effects; Eosinophils; Epinephrine; Immunity; Inflammation; Inflammatory response; Leukocytes (eosinophilic); Lungs; Lymphoid cells; Mice; Nervous system; Rodents; Small intestine
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aan4829

An off switch for helminth immunityGroup 2 innate lymphoid cells (ILC2s) are involved in responses to helminths, viruses, and allergens. Moriyama et al. found that ILC2s interact with the nervous system to modulate helminth immunity. ILC2s from the small intestine expressed the β2-adrenergic receptor (β2AR), which normally interacts with the neurotransmitter epinephrine. Inactivating β2AR resulted in lower helminth burden and more ILC2s, eosinophils, and type 2 cytokine production in mice. Conversely, treatment of helminth-infected mice with a β2AR agonist enhanced worm burden and reduced proliferation of ILC2s. Thus, β2AR negatively regulates ILC2-driven protective immunity.Science, this issue p. 1056The 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.