title: CD11c⁺ CD8⁺ T Cells Reduce Renal Fibrosis Following Ureteric Obstruction by Inducing Fibroblast Apoptosis.
abstract: Tubulointerstitial fibrosis is a common consequence of various kidney diseases that lead to end-stage renal failure, and lymphocyte infiltration plays an important role in renal fibrosis. We previously found that depletion of cluster of differentiation 8⁺ (CD8⁺) T cells increases renal fibrosis following ureteric obstruction, and interferon-γ (IFN-γ)-expressing CD8⁺ T cells contribute to this process. CD8⁺ T cells are cytotoxic T cells; however, whether their cytotoxic effect reduces fibrosis remains unknown. This study showed that CD8⁺ T cells isolated from obstructed kidney showed mRNA expression of the cytotoxicity-related genesperforin 1,granzyme A,granzyme B, andFAS ligand; additionally, CD8 knockout significantly reduced the expression levels of these genes in obstructed kidney. Infiltrated CD8⁺ T cells were distributed around fibroblasts, and they are associated with fibroblast apoptosis in obstructed kidney. Moreover, CD11c⁺ CD8⁺ T cells expressed higher levels of the cytotoxicity-related genes than CD11c-CD8⁺ T cells, and infiltrated CD11c⁺ CD8⁺ T cells in obstructed kidney could induce fibroblast death in vitro. Results indicated that induction of fibroblast apoptosis partly contributed to the effect of CD8⁺ T cells on reduction of renal fibrosis. Given that inflammatory cells are involved in fibrosis, our results suggest that kidney fibrosis is a multifactorial process involving different arms of the immune system.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China. whd1232123@163.com.|College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China. whd1232123@163.com.
authors.forename: Haidong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Tongji Hospital of Shanghai affiliated to Tongji University, Shanghai 20065, China. wangjunshanghai@163.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China. by15110692544@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
authors.affiliation: College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China. 18335442405@163.com.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China. m15534992431@163.com.
authors.forename: Lixin
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China. yanjund@cau.edu.cn.|The Beijing Institute of Heart Lung and Blood Vessel Diseases, Chaoyang, Beijing 100029, China. yanjund@cau.edu.cn.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism*; D014524:Urethral Obstruction / Q000150:complications / Q000378:metabolism*
chemical_list: D039521:CD11c Antigen; D053222:Fas Ligand Protein; D054353:Perforin; D053804:Granzymes
keywords: T cells; fibroblasts; fibrosis; inflammation; kidney