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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\u2013infected mice, which suggested that IL-21 and IL-21R were involved in host defense against C. muridarum lung infection. IL-21R\u2212\/\u2212 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\u2212\/\u2212 mice were significantly higher than those in WT mice after C. muridarum lung infection, but the Th2 response was weaker. Consistently, IL-21R\u2212\/\u2212 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-\u03b2 in IL-21R\u2212\/\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.2001107","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T17:25:41Z","timestamp":1613755541000},"page":"1586-1596","source":"Crossref","is-referenced-by-count":11,"title":["IL-21\/IL-21R Signaling Aggravated Respiratory Inflammation Induced by Intracellular Bacteria through Regulation of CD4+ T Cell Subset Responses"],"prefix":"10.1093","volume":"206","author":[{"given":"Wenhao","family":"Niu","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin 300070 ,","place":["People\u2019s Republic of 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