| First Author | Ajendra J | Year | 2020 |
| Journal | Mucosal Immunol | Volume | 13 |
| Issue | 6 | Pages | 958-968 |
| PubMed ID | 32636457 | Mgi Jnum | J:320887 |
| Mgi Id | MGI:6864376 | Doi | 10.1038/s41385-020-0318-2 |
| Citation | Ajendra J, et al. (2020) IL-17A both initiates, via IFNgamma suppression, and limits the pulmonary type-2 immune response to nematode infection. Mucosal Immunol 13(6):958-968 |
| abstractText | 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 IFNgamma protein production in lung lymphocyte populations. Depletion of early IFNgamma rescued type-2 immune responses in the Il17a-KO mice demonstrating that IL-17A-mediated suppression of IFNgamma 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 IFNgamma 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. |
