The abnormal expression and effects of CD38 positive natural killer cells in rheumatoid arthritis
10.3760/cma.j.issn.1008-1372.2019.09.011
- VernacularTitle: CD38阳性自然杀伤细胞在类风湿关节炎的表达和作用机制
- Author:
Wenping PAN
1
;
Qing WANG
1
;
Xiaohui WANG
2
;
Xiuhua WANG
1
;
Longtao YUE
3
;
Shufeng LI
4
;
Xiaotian CHANG
3
Author Information
1. Department of Rheumatology, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, China
2. Department of Rheumatology, the Second People′s Hospital of Rizhao, Rizhao 276807, China
3. Medical Research Center, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, China
4. Department of Orthopedics, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, China
- Publication Type:Journal Article
- Keywords:
Killer cells, natural;
ADP-ribosyl cyclase 1;
Lymphocyte subsets;
Arthritis, rheumatoid
- From:
Journal of Chinese Physician
2019;21(9):1330-1335
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the distribution of natural killer (NK) cells and the CD38 positive subpopulations in different tissues in rheumatoid arthritis (RA) patients and the mechanism of CD38 agonist.
Methods:The levels of NK cells, CD38 positive subpopulation and NK cell surface chemokine receptors (CXCR3, CCR5), as well as granzyme B and perforin were detected by flow cytometry in peripheral blood and knee synovial fluid. The isolated cells were then cultured in vitro and divided into 3 groups, namely blank control group, IB4 stimulation group (Anti-CD38 mAb), IL-2 and IB4 co-stimulation group. And the concentration of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in culture supernatants was determined by enzyme linked immunosorbent assay (ELISA). Liposome CD38-siRNA was transfected into peripheral blood lymphocytes of RA patients, and transfection efficiency was detected by reverse transcription-polymerase chain reaction (RT-PCR). The effect of CD38 and CD38-siRNA silencing on the expression of phospholipase C-gamma 1 (PLC-γ1) protein in the peripheral blood lymphocytes of RA was detected by Western blot.
Results:The expression of CCR5 and CXCR3 in NK cells in peripercal NK cells of RA was significantly higher than that in normal healthy subjects (P<0.05). The two chemokine receptors (CXCR3, CCR5) were mainly expressed in CD38+ NK cell subsets. The levels of granzyme B and perforin in synovial lymphocytes cells were significantly higher than those in peripheral blood lymphocytes (P<0.05). The secretion of IL-6 and TNF-α in synovial and peripheral blood lymphocytes cells existed significant difference only in IL-2 and IB4 co-stimulation group (P<0.05). The levels of PLC-γ1 protein in the peripheral blood lymphocytes of RA patients was significantly decreased than that in the blank control group after the treatment with CD38-siRNA (P<0.05).
Conclusions:The synovial NK cells are more lethal than the peripheral NK cells in the RA patients. CD38 might mediate the phosphorylation of intracellular proteins via the Protain kinase C (PKC) pathway. Blocking CD38 molecules can reduce the phosphorylation level of intracellular proteins. CD38 maybe involved in the mechanism of chemotaxis and killing capability of NK cells.
