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

Autor: Yongci Zhang, Wenhao Niu, Lida Sun, Lu Tan, Huili Zhao, Tengli Liu, Shuaini Yang, Gaoju Pang, Jiajia Zeng, Hong Bai, Sai Qiao, Yueyue Xu, Hong Zhang, Xiaoyu Zha, Ningbo Zheng
Rok vydání: 2021
Předmět:
Zdroj: The Journal of Immunology. 206:1586-1596
ISSN: 1550-6606
0022-1767
Popis: 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 infection in C57BL/6 mice and reduced Th1 and Th17 responses following C. muridarum lung infection. These findings demonstrate that IL-21/IL-21R may aggravate chlamydial lung infection by inhibiting Th1 and Th17 responses.
Databáze: OpenAIRE
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