IL-21/IL-21R Signaling Aggravated Respiratory Inflammation Induced by Intracellular Bacteria through Regulation of CD4+ T Cell Subset Responses

作者：Wen-Hao Niu, Yue-Yue Xu, Xiaoyu Zha, Jiajia Zeng, Sai Qiao, Shuaini Yang, Hong Zhang, Lu Tan, Li-Da Sun, Gaoju Pang, Tengli Liu, Hui-Li Zhao, Ning-Bo Zheng, Yong-Ci Zhang, Hong Bai · 发表于：Journal of Immunology · 年份：2021 · DOI：10.4049/jimmunol.2001107 · 被引用次数：10 · 研究领域：Medicine

Key Points IL-21/IL-21R can aggravate C. muridarum lung infection. IL-21/IL-21R can suppress Th1/Th17 cell responses in C. muridarum lung infection. The IL-21/IL-21R interaction plays an important role in a variety of immune diseases; however, the roles and mechanisms in intracellular bacterial infection are not fully understood. In this study, we explored the effect of IL-21/IL-21R on chlamydial respiratory tract infection using a chlamydial respiratory infection model. The results showed that the mRNA expression of IL-21 and IL-21R was increased in Chlamydia muridarum–infected mice, which suggested that IL-21 and IL-21R were involved in host defense against C. muridarum lung infection. IL-21R−/− mice exhibited less body weight loss, a lower bacterial burden, and milder pathological changes in the lungs than wild-type (WT) mice during C. muridarum lung infection. The absolute number and activity of CD4+ T cells and the strength of Th1/Th17 responses in IL-21R−/− mice were significantly higher than those in WT mice after C. muridarum lung infection, but the Th2 response was weaker. Consistently, IL-21R−/− mice showed higher mRNA expression of Th1 transcription factors (T-bet/STAT4), IL-12p40, a Th17 transcription factor (STAT3), and IL-23. The mRNA expression of Th2 transcription factors (GATA3/STAT6), IL-4, IL-10, and TGF-β in IL-21R−/− mice was significantly lower than that in WT mice. Furthermore, the administration of recombinant mouse IL-21 aggravated chlamydial lung inf...