Liling Zhao1, Wenwen Xu2, Zhilei Chen3, Haoze Zhang2, Shuo Zhang3, Chaofeng Lian4, Jinlei Sun4, Hua Chen5, Fengchun Zhang6. 1. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing; and Department of Rheumatology and Clinical Immunology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China. 2. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing; and Department of Rheumatology and Clinical Immunology, South Campus, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. 3. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China. 4. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing; and Department of Rheumatology and Clinical Immunology, The First Af liated Hospitalof Zhengzhou University, Zhengzhou, China. 5. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China. chenhua@pumch.cn. 6. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China. zhangfccra@aliyun.com.
Abstract
OBJECTIVES: To elucidate the potential role of CD3+CD56+ NKT-like cells in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: We enrolled pSS patients and healthy controls and examined the peripheral population, the surface chemokine receptors and the proinflammatory cytokine production of NKT-like cells by flow cytometry. The infiltration of NKT-like cells in the labial salivary gland (LSG) was examined by immunofluorescence. Serum and tissue levels of CX3CL1 were detected by Cytometric Bead Array and immunohistochemistry, respectively. The chemotaxis of NKT-like cells was examined by transwell migration assay. RESULTS: Peripheral NKT-like cells from pSS patients were significantly lower than those from HC (3.09±2.35% vs. 5.37±4.06%, p=0.0002), which was negatively correlated with European League Against Rheumatism Sjögren's Syndrome Disease Activity index. NKT-like cells infiltrated into the LSG of pSS patients. Serum and LSG epithelial CX3CL1 levels were higher in pSS patients than those in HC, which promoted the chemotaxis of the NKT-like cells. NKT-like cells from pSS patients expressed a higher level of CD69, and secreted high level of TNF-α and IFN-γ, which was promoted by CX3CL1 in vitro. CONCLUSIONS: NKT-like cells decreased in peripheral and infiltrated into the LSG of the pSS patients, which could be driven by CX3CL1-CX3CR1 axis. NKT-like cells might be implicated in the pathogenesis of pSS.
OBJECTIVES: To elucidate the potential role of CD3+CD56+ NKT-like cells in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: We enrolled pSS patients and healthy controls and examined the peripheral population, the surface chemokine receptors and the proinflammatory cytokine production of NKT-like cells by flow cytometry. The infiltration of NKT-like cells in the labial salivary gland (LSG) was examined by immunofluorescence. Serum and tissue levels of CX3CL1 were detected by Cytometric Bead Array and immunohistochemistry, respectively. The chemotaxis of NKT-like cells was examined by transwell migration assay. RESULTS: Peripheral NKT-like cells from pSS patients were significantly lower than those from HC (3.09±2.35% vs. 5.37±4.06%, p=0.0002), which was negatively correlated with European League Against Rheumatism Sjögren's Syndrome Disease Activity index. NKT-like cells infiltrated into the LSG of pSS patients. Serum and LSG epithelial CX3CL1 levels were higher in pSS patients than those in HC, which promoted the chemotaxis of the NKT-like cells. NKT-like cells from pSS patients expressed a higher level of CD69, and secreted high level of TNF-α and IFN-γ, which was promoted by CX3CL1 in vitro. CONCLUSIONS: NKT-like cells decreased in peripheral and infiltrated into the LSG of the pSS patients, which could be driven by CX3CL1-CX3CR1 axis. NKT-like cells might be implicated in the pathogenesis of pSS.