IL-17A both initiates, via IFNγ suppression, and limits the pulmonary type 2 immune response to nematode infection

Jesuthas Ajendra, Alistair Chenery, James Parkinson, B.H.K Chan, Stella Pearson, Stefano Colombo, Louis Boon, Richard Grencis, Tara Sutherland, Judith Allen

Research output: Contribution to journalArticlepeer-review


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 Ifn γ signature in Il17a-KO mice confirmed by enhanced IFN γ 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 IFN γ 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.
Original languageEnglish
Pages (from-to)958–968
Number of pages10
JournalMucosal Immunology
Publication statusPublished - 7 Jul 2020


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