{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:39:05Z","timestamp":1778827145673,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31870889"],"award-info":[{"award-number":["31870889"]}]},{"name":"National Natural Science Foundation of China","award":["31070797"],"award-info":[{"award-number":["31070797"]}]},{"name":"National Natural Science Foundation of China","award":["19JCZDJC35800"],"award-info":[{"award-number":["19JCZDJC35800"]}]},{"name":"National Natural Science Foundation of China","award":["15JCZDJC34900"],"award-info":[{"award-number":["15JCZDJC34900"]}]},{"name":"Key Program of Tianjin Science and Technology Commission","award":["31870889"],"award-info":[{"award-number":["31870889"]}]},{"name":"Key Program of Tianjin Science and Technology Commission","award":["31070797"],"award-info":[{"award-number":["31070797"]}]},{"name":"Key Program of Tianjin Science and Technology Commission","award":["19JCZDJC35800"],"award-info":[{"award-number":["19JCZDJC35800"]}]},{"name":"Key Program of Tianjin Science and Technology Commission","award":["15JCZDJC34900"],"award-info":[{"award-number":["15JCZDJC34900"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interleukin-21 and its receptors (IL-21\/IL-21R) aggravate chlamydial lung infection, while macrophages (M\u03c6) are one of the main cells infected by chlamydia and the main source of inflammatory cytokines. Therefore, it is particularly important to study whether IL-21\/IL-21R aggravates chlamydia respiratory infection by regulating M\u03c6. Combined with bioinformatics analysis, we established an IL-21R-deficient (IL-21R\u2212\/\u2212) mouse model of Chlamydia muridarum (C. muridarum) respiratory tract infection in vivo, studied C. muridarum-stimulated RAW264.7 by the addition of rmIL-21 in vitro, and conducted adoptive transfer experiments to clarify the association between IL-21\/IL-21R and M\u03c6. IL-21R\u2212\/\u2212 mice showed lower infiltration of pulmonary total M\u03c6, alveolar macrophages, and interstitial macrophages compared with WT mice following infection. Transcriptomic analysis suggested that M1-related genes are downregulated in IL-21R\u2212\/\u2212 mice and that IL-21R deficiency affects the M\u03c6-mediated inflammatory response during C. muridarum infection. In vivo experiments verified that in IL-21R\u2212\/\u2212 mice, pulmonary M1-type CD80+, CD86+, MHC II+, TNF\u03b1+, and iNOS+ M\u03c6 decreased, while there were no differences in M2-type CD206+, TGF-\u03b2+, IL-10+ and ARG1+ M\u03c6. In vitro, administration of rmIL-21 to C. muridarum-stimulated RAW264.7 cells promoted the levels of iNOS-NO and the expression of IL-12p40 and TNF\u03b1, but had no effect on TGF\u03b2 or IL-10. Further, adoptive transfer of M1-like bone marrow-derived macrophages derived from IL-21R\u2212\/\u2212 mice, unlike those from WT mice, effectively protected the recipients against C. muridarum infection and induced relieved pulmonary pathology. These findings help in understanding the mechanism by which IL-21\/IL-21R exacerbates chlamydia respiratory infection by promoting the proinflammatory effect of M\u03c6.<\/jats:p>","DOI":"10.3390\/ijms241612557","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:26:39Z","timestamp":1691497599000},"page":"12557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["IL-21\/IL-21R Promotes the Pro-Inflammatory Effects of Macrophages during C. muridarum Respiratory Infection"],"prefix":"10.3390","volume":"24","author":[{"given":"Shuaini","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajia","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlian","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoyuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Tuo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Tan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.tim.2020.05.020","article-title":"Chlamydiae in the Environment","volume":"28","author":"Collingro","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1177\/0300985817751218","article-title":"A Review on Chlamydial Diseases in Animals: Still a Challenge for Pathologists?","volume":"55","author":"Borel","year":"2018","journal-title":"Vet. 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