IL-17A both initiates, via IFNγ suppression, and limits the pulmonary type-2 immune response to nematode infection
Chenery, Alistair L.
Parkinson, James E.
Chan, Brian H. K.
Colombo, Stefano A. P.
Grencis, Richard K.
Sutherland, Tara E.; email: firstname.lastname@example.org
Allen, Judith E.; orcid: 0000-0002-3829-066X; email: email@example.com
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AbstractAbstract: Nippostrongylus brasiliensis is a well-defined model of type-2 immunity but the early lung-migrating phase is dominated by innate IL-17A production. In this study, we confirm previous observations that Il17a-KO mice infected with N. brasiliensis exhibit an impaired type-2 immune response. Transcriptional profiling of the lung on day 2 of N. brasiliensis infection revealed an increased Ifng signature in Il17a-KO mice confirmed by enhanced IFNγ protein production in lung lymphocyte populations. Depletion of early IFNγ rescued type-2 immune responses in the Il17a-KO mice demonstrating that IL-17A-mediated suppression of IFNγ promotes type-2 immunity. Notably, later in infection, once the type-2 response was established, IL-17A limited the magnitude of the type-2 response. IL-17A regulation of type-2 immunity was lung-specific and infection with Trichuris muris revealed that IL-17A promotes a type-2 immune response in the lung even when infection is restricted to the intestine. Together our data reveal IL-17A as a major regulator of pulmonary type-2 immunity such that IL-17A supports early development of a protective type-2 response by suppression of IFNγ but subsequently limits excessive type-2 responses. A failure of this feedback loop may contribute to conditions such as severe asthma, characterised by combined elevation of IL-17 and type-2 cytokines.
CitationMucosal Immunology, volume 13, issue 6, page 958-968
PublisherNature Publishing Group US
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2020-04-17, rev-recd 2020-05-21, accepted 2020-06-09, registration 2020-06-19, pub-electronic 2020-07-07, online 2020-07-07, pub-print 2020-11
Publication status: Published