Local sympathetic innervations modulate the lung innate immune responses
Open Access
- 1 May 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (20), eaay1497
- https://doi.org/10.1126/sciadv.aay1497
Abstract
Local immunity of the lung needs to be under tight control. However, how efferent neural signals influence lung immunity remains incompletely understood. Here, we report the development of a modified iDISCO-based protocol, iDISCO(ace), for whole-tissue 3D assessment of neural innervations and immune reactions in intact, unsectioned lung tissues. We observed that genetic, pharmacologic, or surgical removal of local sympathetic innervations promoted LPS-elicited innate immune response in the lung. Also, sympathetic ablation enhanced IL-33-elicited type 2 innate immunity. We further show that the sympathetic neurotransmitter norepinephrine, or specific agonists of the beta 2-adrenergic receptor, can inhibit the LPS- or IL-33-elicited immune response in a cell-intrinsic manner. Moreover, genetic deletion of the beta 2-adrenergic receptor produced immunomodulatory effects similar to those observed with sympathetic ablation. Together, this study elucidates the critical function of local sympathetic innervations in negatively modulating the lung innate immune responses.Funding Information
- National Natural Science Foundation of China (31522024)
- National Natural Science Foundation of China (31771111)
- National Natural Science Foundation of China (31970974)
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