Anipindi Varun C, Bagri Puja, Dizzell Sara E, Jiménez-Saiz Rodrigo, Jordana Manel, Snider Denis P, Stämpfli Martin R, Kaushic Charu
McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8S 4K1, Canada; and.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Immunohorizons. 2019 Jul 17;3(7):317-330. doi: 10.4049/immunohorizons.1900040.
IL-17 can be produced by adaptive immune cells such as T17 cells and by immune cells that produce IL-17 without prior priming. This latter category, which we will refer to as "innate," includes innate cells such as NK cells and innate lymphoid cells and innate-like T cell populations such as NKT cells and γδ T cells. Studies in mucosal tissues have shown that the induction of T17 immunity is amplified by innate IL-17 produced within those tissues. However, the role of innate IL-17 and its effect on T17 induction in the female genital tract (FGT) is largely unknown. In this study, we characterize the primary source of IL-17-secreting vaginal cells and show that innate IL-17 plays a critical role in priming adaptive T17 responses in the FGT. Under homeostatic conditions, γδ T cells were the predominant source of innate IL-17 in the murine FGT, and this population was modulated by both the sex hormone estradiol and the presence of commensal microbiota. Compared with wild-type C57BL/6 mice, vaginal APCs isolated from IL-17A-deficient ( ) mice were severely impaired at priming T17 responses in APC-T cell cocultures. Furthermore, the defect in T17 induction in the absence of innate IL-17 was associated with impairment of IL-1β production by vaginal CD11c dendritic cells. Overall, our study describes a novel role for IL-17 in the FGT and further demonstrates the importance of factors in the vaginal microenvironment that can influence adaptive immune responses.
白细胞介素-17（IL-17）可由适应性免疫细胞如T17细胞产生，也可由无需预先致敏就能产生IL-17的免疫细胞产生。后一类细胞，我们将其称为“固有免疫细胞”，包括固有免疫细胞如自然杀伤细胞（NK细胞）和固有淋巴细胞，以及固有样T细胞群体如自然杀伤T细胞（NKT细胞）和γδT细胞。对黏膜组织的研究表明，这些组织中产生的固有IL-17可放大T17免疫的诱导。然而，固有IL-17在女性生殖道（FGT）中的作用及其对T17诱导的影响在很大程度上尚不清楚。在本研究中，我们对分泌IL-17的阴道细胞的主要来源进行了表征，并表明固有IL-17在启动FGT中的适应性T17反应中起关键作用。在稳态条件下，γδT细胞是小鼠FGT中固有IL-17的主要来源，该群体受性激素雌二醇和共生微生物群的存在的调节。与野生型C57BL/6小鼠相比，从IL-17A缺陷（ ）小鼠分离的阴道抗原呈递细胞（APC）在APC-T细胞共培养中启动T17反应时严重受损。此外，在缺乏固有IL-17的情况下T17诱导的缺陷与阴道CD11c树突状细胞产生IL-1β的受损有关。总体而言，我们的研究描述了IL-17在FGT中的新作用，并进一步证明了阴道微环境中可影响适应性免疫反应的因素的重要性。
