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.

Nippostrongylus brasiliensis是一种定义明确的 2 型免疫模型，但早期肺迁移阶段主要是先天性 IL-17A 的产生。在这项研究中，我们证实了先前的观察结果，即感染巴西橡胶树的 Il17a -KO 小鼠表现出受损的 2 型免疫反应。巴西橡胶树感染第 2 天的肺转录分析显示Il17a -KO 小鼠的Ifng 特征增加，这由肺淋巴细胞群中 IFNγ 蛋白生成的增强得到证实。早期 IFNγ 的消耗挽救了Il17a中的 2 型免疫反应-KO 小鼠证明 IL-17A 介导的 IFNγ 抑制可促进 2 型免疫。值得注意的是，在感染后期，一旦建立了 2 型反应，IL-17A 就会限制 2 型反应的强度。IL-17A 对 2 型免疫的调节是肺特异性的，鼠鞭虫感染表明 IL-17A 促进肺中的 2 型免疫反应，即使感染仅限于肠道。我们的数据共同揭示了 IL-17A 作为肺 2 型免疫的主要调节因子，因此 IL-17A 通过抑制 IFNγ 支持保护性 2 型反应的早期发展，但随后限制过度的 2 型反应。这种反馈回路的失败可能导致严重哮喘等病症，其特征是 IL-17 和 2 型细胞因子的联合升高。