title: Downregulation of IL-10 secretion by Treg cells in osteoarthritis is associated with a reduction in Tim-3 expression.
abstract: Knee osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability in the knee. Though traditionally thought a mechanical wear-and-tear disease, in recent years, knee OA as a low-grade, chronic inflammatory disease has been increasingly recognized. In this study, we examined the Treg responses in non-obese knee OA patients at different stages. Significantly elevated frequencies of CD4(+)CD25(+)Foxp3(+) Tregs were found in OA patients, while on the other hand, lower IL-10 secretion from Tregs in OA patients was observed. Importantly, this decrease in IL-10 was associated with reduced Tim-3 expression on Tregs. Although both Tim-3(-) and Tim3(+) Tregs could secrete IL-10, the majority of IL-10 was observed in Tim-3(+) Tregs. Reduction of Tim-3(+) Tregs in OA patients resulted in less IL-10-producing Tregs. Interestingly, the OA patients in more advanced stages showed further reductions in IL-10 and Tim-3 expression. In conclusion, our results revealed an immunoregulatory disorder in OA independent of obesity, and demonstrated a potential mechanism in establishing the proinflammatory status of OA patients.
authors.affiliation: Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University, 16766 Jing Shi Road, Jinan, Shandong 250014, China. Electronic address: shufenglisd@126.com.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Zhengzhou Hospital, Zhengzhou, Henan, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Wan
authors.affiliation: Research Center, BGC Biotechnology, Vancouver, BC, Canada.
authors.forename: William
authors.initials: W
authors.lastname: Anderson
authors.affiliation: Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University, 16766 Jing Shi Road, Jinan, Shandong 250014, China.
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University, 16766 Jing Shi Road, Jinan, Shandong 250014, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University, 16766 Jing Shi Road, Jinan, Shandong 250014, China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University, 16766 Jing Shi Road, Jinan, Shandong 250014, China.
authors.forename: Zhaolong
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University, 16766 Jing Shi Road, Jinan, Shandong 250014, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University, 16766 Jing Shi Road, Jinan, Shandong 250014, China. Electronic address: drxinfengyan@sina.com.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Yan
authors.affiliation: Research Center, BGC Biotechnology, Vancouver, BC, Canada.
authors.forename: Wendy
authors.initials: W
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D016022:Case-Control Studies; D003710:Demography; D015536:Down-Regulation; D005260:Female; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C508609:IL10 protein, human; D016753:Interleukin-10
keywords: IL-10; Osteoarthritis; Treg