Manman Liu1,2, Junli Liu3, Xiaoyan Zhang1, Yichuan Xiao3, Gengru Jiang1, Xinfang Huang4,5. 1. Department of Renal and Rheumatology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. 2. Department of Rheumatology and Immunology, Nanjing Jiangning Hospital, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 211100, China. 3. The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. 4. Department of Renal and Rheumatology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. huangxinfang@xinhuamed.com.cn. 5. Department of Rheumatology, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China. huangxinfang@xinhuamed.com.cn.
Abstract
OBJECTIVES: Decreased natural killer (NK) cells have been reported in systemic lupus erythematosus (SLE) patients. However, the role of NK cells in the pathogenesis of SLE is not well understood. In this study, we aimed to characterize NK cell subsets, phenotypes, and cytokine-secreting functions and investigate the clinical relevance of NK cells in SLE patients. METHODS: Peripheral blood samples from 81 SLE patients and 59 healthy donors (HDs) were collected. The frequency and phenotype of NK cells were measured by flow cytometry. Intracellular interferon-γ (IFN-γ) production by NK cells was evaluated by flow cytometry after stimulation with interleukin-12 (IL-12) and IL-18. RESULTS: The percentages of NK cells in the peripheral blood of SLE patients were significantly lower than those in HDs, and the percentages of CD56dim NK cells among total NK cells showed a trend toward decrease. The CD56dim NK cells in SLE patients showed increased production of IFN-γ and displayed relatively activated phenotypic characteristics, including significant increases in NKp44, NKp46, and CD69 and decreased expression of CD16 and CD158a/h/g. Furthermore, CD56dim NK cells in active SLE patients had higher percentages of NKp44+ cells and lower percentages of CD158a/h/g+ cells than those in inactive SLE patients. The percentages of CD158a/h/g+ cells among CD56dim NK cells were negatively correlated with the systemic lupus erythematosus disease activity index (SLEDAI) and positively correlated with C3 and C4 levels. CONCLUSION: CD56dim NK cells in SLE patients show a reduced proportion tendency among total NK cells and are activated, which partially reflects the disease activity. CD158a/h/g expression on CD56dim NK cells may be considered an index of disease activity. Key Points • In patients with SLE, the proportion of CD56dim NK cells showed a decreased trend and CD56dim NK cells were phenotypically activated which partially reflects the disease activity. • CD158a/h/g expression on CD56dim NK cells were decreased which may be used as an indicator for evaluating disease activity in SLE patients.
OBJECTIVES: Decreased natural killer (NK) cells have been reported in systemic lupus erythematosus (SLE) patients. However, the role of NK cells in the pathogenesis of SLE is not well understood. In this study, we aimed to characterize NK cell subsets, phenotypes, and cytokine-secreting functions and investigate the clinical relevance of NK cells in SLEpatients. METHODS: Peripheral blood samples from 81 SLEpatients and 59 healthy donors (HDs) were collected. The frequency and phenotype of NK cells were measured by flow cytometry. Intracellular interferon-γ (IFN-γ) production by NK cells was evaluated by flow cytometry after stimulation with interleukin-12 (IL-12) and IL-18. RESULTS: The percentages of NK cells in the peripheral blood of SLEpatients were significantly lower than those in HDs, and the percentages of CD56dim NK cells among total NK cells showed a trend toward decrease. The CD56dim NK cells in SLEpatients showed increased production of IFN-γ and displayed relatively activated phenotypic characteristics, including significant increases in NKp44, NKp46, and CD69 and decreased expression of CD16 and CD158a/h/g. Furthermore, CD56dim NK cells in active SLEpatients had higher percentages of NKp44+ cells and lower percentages of CD158a/h/g+ cells than those in inactive SLEpatients. The percentages of CD158a/h/g+ cells among CD56dim NK cells were negatively correlated with the systemic lupus erythematosus disease activity index (SLEDAI) and positively correlated with C3 and C4 levels. CONCLUSION: CD56dim NK cells in SLEpatients show a reduced proportion tendency among total NK cells and are activated, which partially reflects the disease activity. CD158a/h/g expression on CD56dim NK cells may be considered an index of disease activity. Key Points • In patients with SLE, the proportion of CD56dim NK cells showed a decreased trend and CD56dim NK cells were phenotypically activated which partially reflects the disease activity. • CD158a/h/g expression on CD56dim NK cells were decreased which may be used as an indicator for evaluating disease activity in SLEpatients.
Authors: Gloria Yiu; Tue Kruse Rasmussen; Brandon L Tsai; Vivian K Diep; David J Haddon; Jennifer Tsoi; Gopika D Miller; Begoña Comin-Anduix; Bent Deleuran; Gay M Crooks; Paul J Utz Journal: Front Immunol Date: 2022-01-28 Impact factor: 7.561