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

By Jesuthas Ajendra, Alistair L Chenery, James E Parkinson, Brian H. K. Chan, Stella Pearson, Stefano A. P. Colombo, Louis Boon, Richard K. Grencis, Tara E. Sutherland, Judith E. Allen

Posted 01 Nov 2019
bioRxiv DOI: 10.1101/827899 (published DOI: 10.1038/s41385-020-0318-2)

Nippostrongylus brasiliensis is a well-defined model of type-2 immunity but the early lung-migrating phase is dominated by innate IL-17A production and neutrophilia. Using N. brasiliensis infection we confirm previous observations that Il17a-KO mice exhibit an impaired type-2 immune response. Neutrophil depletion and reconstitution studies demonstrated that neutrophils contribute to the subsequent eosinophilia but are not responsible for the ability of IL-17A to promote type-2 cytokine responses. Transcriptional profiling of the lung on day 2 of N. brasiliensis infection revealed an increased Ifnγ signature in the Il17a-KO mice confirmed by enhanced IFNγ protein production. 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, when IL-17A was blocked later in infection, the type-2 response increased. 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 a parasite lifecycle is restricted to the intestine. Together our data reveal IL-17A as a major regulator of pulmonary type-2 immunity which supports the development of a protective type-2 immune response but subsequently limits the magnitude of that response. ### Competing Interest Statement The authors have declared no competing interest.

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