title: Effects of 1,25(OH)2D3and vitamin D receptor on peripheral CD4+/CD8+double-positive T lymphocytes in a mouse model of systemic lupus erythematosus.
abstract: This study aims to explore effects of 1,25(OH)2D3and vitamin D receptor (VDR) on peripheral CD4+/CD8+double-positive (DP) T lymphocytes in systemic lupus erythematosus (SLE). MRL-LPr/LPr mice with SLE (n = 20) and normal MRL mice (n = 20) were assigned into the control group (normal mice, without feeding with 1,25(OH)2D3), the 1,25(OH)2D3group (SLE mice, feeding with 1,25(OH)2D3), the VDR-knock-in + 1,25(OH)2D3group (SLE mice, VDR-knock-in, feeding with 1,25(OH)2D3) and the VDR-knockout group (normal mice, VDR-knockout, without feeding with 1,25(OH)2D3) (n = 10 per group). Levels of T lymphocytes were measured by flow cytometry. The mRNA and proteins expressions of inflammatory factors were measured by qRT-PCR and ELISA. Extracellular signal-regulated kinase-1/2 (ERK1/2) expression was measured by Western blotting. Compared with normal mice, SLE mice showed reduced levels of CD4+, CD4+/CD8+ratio, and DP lymphocytes. The levels of SLE-related indicators all increased significantly, followed with severe skin ulcers and urinary system infection. With the increase in time, skin ulcers and urinary system infection were significantly improved, levels of CD4+, CD4+/CD8+ratio, and DP lymphocytes increased, and levels of SLE-related indicators all decreased in the 1,25(OH)2D3group. There were no significant changes in bioindicators in the control and the VDR-knock-in + 1,25(OH)2D3groups. The symptoms of SLE gradually occurred in the VDR-knockout group. This study demonstrates that VDR and 1,25(OH)2D3could elevate CD4+/CD8+DP T lymphocytes and reduce expressions of inflammatory factors, thus inhibiting the development and progression of SLE.
authors.affiliation: Department of Dermatology, Maternal and Child Health Care Hospital of Hainan Province, Haikou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Hainan General Hospital, Haikou, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, China.|Laboratory of Pediatric Nephrology, Institute of Pediatrics, Central South University, Changsha, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: He
authors.affiliation: Department of Pediatrics, Maternal and Child Health Care Hospital of Hainan Province, Haikou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002117:Calcitriol / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D019463:Mice, Inbred MRL lpr; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D048049:Extracellular Signal-Regulated MAP Kinases; D002117:Calcitriol
keywords: 1,25(OH)2D3; CD4+; CD8+; T lymphocytes; mouse model; systemic lupus erythematosus; vitamin D receptor