Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths

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

doi:10.1126/sciimmunol.abd0359

Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths

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

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Abstract

Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated. Group 2 ILCs (ILC2s) are shown here to synthesize 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-33 (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, lower numbers of ILC2s, and reduced lung and gut barrier responses to Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in the expansion of ILC2s for maximal induction of type 2 immunity.

Original language	English
Article number	eabd0359
Journal	Science Immunology
Volume	6
Issue number	57
DOIs	https://doi.org/10.1126/sciimmunol.abd0359
Publication status	Published - 5 Mar 2021

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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RobertsLB2021Acetylcholine
This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Immunology on 05 Mar 2021: Vol. 6, Issue 57, eabd0359, DOI: 10.1126/sciimmunol.abd0359.
Accepted author manuscript, 1.84 MBLicence: None: All rights reserved

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Roberts, L. B., Schnoeller, C., Berkachy, R., Darby, M., Pillaye, J., Oudhoff, M. J., Parmar, N., Mackowiak, C., Sedda, D., Quesniaux, V., Ryffel, B., Vaux, R., Gounaris, K., Berrard, S., Withers, D. R., Horsnell, W. G. C., & Selkirk, M. E. (2021). Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths. Science Immunology, 6(57), Article eabd0359. https://doi.org/10.1126/sciimmunol.abd0359

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title = "Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths",

abstract = "Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated. Group 2 ILCs (ILC2s) are shown here to synthesize 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-33 (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, lower numbers of ILC2s, and reduced lung and gut barrier responses to Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in the expansion of ILC2s for maximal induction of type 2 immunity.",

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

note = "Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2021",

month = mar,

day = "5",

doi = "10.1126/sciimmunol.abd0359",

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Roberts, LB, Schnoeller, C, Berkachy, R, Darby, M, Pillaye, J, Oudhoff, MJ, Parmar, N, Mackowiak, C, Sedda, D, Quesniaux, V, Ryffel, B, Vaux, R, Gounaris, K, Berrard, S, Withers, DR, Horsnell, WGC & Selkirk, ME 2021, 'Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths', Science Immunology, vol. 6, no. 57, eabd0359. https://doi.org/10.1126/sciimmunol.abd0359

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AU - Roberts, Luke B

AU - Schnoeller, Corinna

AU - Berkachy, Rita

AU - Darby, Matthew

AU - Pillaye, Jamie

AU - Oudhoff, Menno J

AU - Parmar, Naveen

AU - Mackowiak, Claire

AU - Sedda, Delphine

AU - Quesniaux, Valerie

AU - Ryffel, Bernhard

AU - Vaux, Rachel

AU - Gounaris, Kleoniki

AU - Berrard, Sylvie

AU - Withers, David R

AU - Horsnell, William G C

AU - Selkirk, Murray E

PY - 2021/3/5

Y1 - 2021/3/5

N2 - Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated. Group 2 ILCs (ILC2s) are shown here to synthesize 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-33 (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, lower numbers of ILC2s, and reduced lung and gut barrier responses to Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in the expansion of ILC2s for maximal induction of type 2 immunity.

AB - Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated. Group 2 ILCs (ILC2s) are shown here to synthesize 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-33 (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, lower numbers of ILC2s, and reduced lung and gut barrier responses to Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in the expansion of ILC2s for maximal induction of type 2 immunity.

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DO - 10.1126/sciimmunol.abd0359

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SN - 2470-9468

VL - 6

JO - Science Immunology

JF - Science Immunology

IS - 57

M1 - eabd0359

ER -

Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths

Abstract

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