Differential Regulation of Allergic Airway Inflammation by Acetylcholine.

Autor:	Roberts LB; Department of Life Sciences, Imperial College London, London, United Kingdom.; School of Immunology and Microbial Sciences, King's College London, Great Maze Pond, London, United Kingdom., Berkachy R; Department of Life Sciences, Imperial College London, London, United Kingdom., Wane M; Department of Life Sciences, Imperial College London, London, United Kingdom., Patel DF; National Heart and Lung Institute, Imperial College London, London, United Kingdom., Schnoeller C; Department of Life Sciences, Imperial College London, London, United Kingdom., Lord GM; School of Immunology and Microbial Sciences, King's College London, Great Maze Pond, London, United Kingdom.; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom., Gounaris K; Department of Life Sciences, Imperial College London, London, United Kingdom., Ryffel B; Laboratory of Molecular and Experimental Immunology and Neurogenetics, UMR 7355, CNRS-University of Orleans and Le Studium Institute for Advanced Studies, Rue Dupanloup, Orléans, France., Quesniaux V; Laboratory of Molecular and Experimental Immunology and Neurogenetics, UMR 7355, CNRS-University of Orleans and Le Studium Institute for Advanced Studies, Rue Dupanloup, Orléans, France., Darby M; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Horsnell WGC; Laboratory of Molecular and Experimental Immunology and Neurogenetics, UMR 7355, CNRS-University of Orleans and Le Studium Institute for Advanced Studies, Rue Dupanloup, Orléans, France.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom., Selkirk ME; Department of Life Sciences, Imperial College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 May 27; Vol. 13, pp. 893844. Date of Electronic Publication: 2022 May 27 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.893844
Abstrakt:	Acetylcholine (ACh) from neuronal and non-neuronal sources plays an important role in the regulation of immune responses and is associated with the development of several disease pathologies. We have previously demonstrated that group 2 innate lymphoid cell (ILC2)-derived ACh is required for optimal type 2 responses to parasitic infection and therefore sought to determine whether this also plays a role in allergic inflammation. Rora Cre+ Chat LoxP mice (in which ILC2s cannot synthesize ACh) were exposed to an allergenic extract of the fungus Alternaria alternata , and immune responses in the airways and lung tissues were analyzed. Airway neutrophilia and expression of the neutrophil chemoattractants CXCL1 and CXCL2 were enhanced 24 h after exposure, suggesting that ILC2-derived ACh plays a role in limiting excessive pulmonary neutrophilic inflammation. The effect of non-selective depletion of ACh was examined by intranasal administration of a stable parasite-secreted acetylcholinesterase. Depletion of airway ACh in this manner resulted in a more profound enhancement of neutrophilia and chemokine expression, suggesting multiple cellular sources for the release of ACh. In contrast, depletion of ACh inhibited Alternaria -induced activation of ILC2s, suppressing the expression of IL-5, IL-13, and subsequent eosinophilia. Depletion of ACh reduced macrophages with an alternatively activated M2 phenotype and an increase in M1 macrophage marker expression. These data suggest that ACh regulates allergic airway inflammation in several ways, enhancing ILC2-driven eosinophilia but suppressing neutrophilia through reduced chemokine expression. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Roberts, Berkachy, Wane, Patel, Schnoeller, Lord, Gounaris, Ryffel, Quesniaux, Darby, Horsnell and Selkirk.)
Databáze:	MEDLINE
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