title: Hyperactivation and in situ recruitment of inflammatory Vδ2 T cells contributes to disease pathogenesis in systemic lupus erythematosus.
abstract: In this study, we measured the proportion of peripheral Vδ2 T cells as well as the status and chemokine receptor expression profiles in SLE patients and healthy control (HC). In addition, Vδ2 T cell infiltration in the kidneys of patients with lupus nephritis was examined. The results showed that the percentage of peripheral Vδ2 T cells in new-onset SLE was decreased, and negatively correlated with the SLE Disease Activity Index score and the severity of proteinuria. These cells had a decreased apoptosis but an increased proliferation, and they showed increased accumulation in SLE kidneys. Moreover, IL-21 production and CD40L, CCR4, CCR7, CCR8, CXCR1 and CX3CR1 expression in Vδ2 T cells from SLE patients was significantly higher than from HC (p < 0.05), and these factors were downregulated in association with the repopulation of peripheral Vδ2 T cells in patients who were in remission (p < 0.05). In addition, anti-TCR Vδ2 antibodies activation significantly upregulated these chemokine receptors on Vδ2 T cells from HC, and this effect was blocked by inhibitors of PLC-γ1, MAPK/Erk, and PI3K signaling pathways. Our findings demonstrate that the distribution and function status of Vδ2 T cells from SLE patients are abnormal, and these aberrations may contribute to disease pathogenesis.
authors.affiliation: Department of Rheumatology &Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yin
authors.affiliation: Department of Immunology, School of Basic Medicine, Peking Union Medical College, and Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Yue
authors.affiliation: Department of Rheumatology &Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Rheumatology &Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Linfang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Rheumatology &Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Mo
authors.affiliation: Department of Rheumatology &Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Immunology, School of Basic Medicine, Peking Union Medical College, and Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medicine, Peking Union Medical College, and Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Rheumatology &Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology; D023201:CD40 Ligand / Q000096:biosynthesis; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis; D007668:Kidney / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology*; D008297:Male; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D018925:Chemokines; D007378:Interleukins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011948:Receptors, Antigen, T-Cell; D019707:Receptors, Chemokine; D023201:CD40 Ligand; D048049:Extracellular Signal-Regulated MAP Kinases; D051966:Phospholipase C gamma; D000098546:Interleukin-21