IL-17A both initiates, via IFNγ suppression, and limits the pulmonary type 2 immune response to nematode infection
| Autor: | Jesuthas Ajendra, Alistair Chenery, Parkinson, James E., Brian Chan, Stella Pearson, Stefano Adriano Colombo, Louis Boon, Richard Grencis, Sutherland, Tara E., Judith Allen |
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| Zdroj: | University of Manchester-PURE Ajendra, J, Chenery, A, Parkinson, J, Chan, B H K, Pearson, S, Colombo, S, Boon, L, Grencis, R, Sutherland, T & Allen, J 2020, ' IL-17A both initiates, via IFNγ suppression, and limits the pulmonary type 2 immune response to nematode infection ', Mucosal Immunology, vol. 13, pp. 958–968 . < https://www.nature.com/articles/s41385-020-0318-2 > |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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