Acetylcholine production by type 2 innate lymphoid cells promotes mucosal immunity to helminth parasites

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Roberts, Luke, B | Schnoeller, Corinna | Berkachy, Rita | Darby, Matthew | Pillaye, Jamie | Oudhoff, Menno, J | Parmar, Naveen | Mackowiak, Claire | Sedda, Delphine | Quesniaux, Valérie | Ryffel, Bernhard | Vaux, Rachel | Gounaris, Kleoniki | Berrard, Sylvie | Withers, David, R | Horsnell, William G C | Selkirk, Murray, E

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. While neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently begun to be appreciated. Type 2 innate lymphoid cells (ILC2s) are shown here to synthesise and release acetylcholine (ACh) during parasitic nematode infection. The cholinergic phenotype of pulmonary ILC2s was associated with their activation state, could be induced by in vivo exposure to extracts of Alternaria alternata or the alarmin cytokines interleukin (IL)-33 and IL-25, and was augmented by IL-2 in vitro. Genetic disruption of ACh synthesis by murine ILC2s resulted in increased parasite burdens, impaired ILC2 proliferation, and reduced features of lung and gut barrier responses following Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in expansion of ILC2s for maximal induction of type 2 immunity.

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