Study on the balance rebuilding of regulatory T cells/Th17 cells by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin for the treatment of rheumatoid arthritis / 中华风湿病学杂志

ABSTRACT

Objective To investigate the regulatory T cells (Treg) induced by 2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin (TCDD) on the aryl hydrocarbon receptor activator from na?ve T cells, in collagen-induced arthritis (CIA)-rheumatoid arthritis (RA) mouse in the correction of rheumatoid arthritis pathological process on Th17/Treg cell imbalance. Methods ① Rat CIA model was established by bovine Ⅱ collagen injection. The rats were divided into 3 groups the normal group (N), the CIA model group (C), and the TCDD group (T).② The percentage of Th17 and Treg from peripheral blood mononuclear cells (PBMCs) were analyzed with flow cytometry (FCM). Th17 and Treg cells related cytokine including interleukin (IL)-1β, IL-6, IL-17A, IL-23, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β were measured with enzyme linked immunosorbent assay (ELISA). ③ The changes of the arthritis parameters, and radiological of T/NT before and after treatment were observed. ④ After two weeks of treatment, the rats were killed. The swollen joints were used for pathological assessment and arthritic pathology injury score was evaluated. ⑤ All data were analyzed by one-way analysis of variance (ANOVA) test and t test. Results In group CWhen the second immunization was compared with the first, the percentage of Th17 cells was significantly increased [(2.99 ±0.16)%, (4.02 ± 0.33)%, t=-6.82, P<0.01], while Treg cells were significantly reduced [(2.67 ±0.57)%, (1.79 ±0.39)%, t=3.11, P=0.000], Th17/Treg was significantly increased (1.14 ±0.14, 2.27 ±0.39, t=-4.53, P=0.039). In group T, the percentage of Th17 cells were significantly reduced [(2.69±0.24)%, (1.21±0.25)%, t=5.12, P<0.01] before and after treatment, while Treg cells were significantly increased [(2.76 ±0.36)%, (3.78 ±0.22)%, t=-6.24, P<0.01], Th17/Treg was significantly reduced (1.08±0.07, 0.21±0.05, t=-11.92, P=0.027). In group CWhen the second immunization was compared with the first, the Th17 cells related cytokines were significantly increased inclu-ding IL-1 [(96±12) pg/ml, (153±18) pg/ml, t=-13.24, P<0.01], IL-6 [(246±14) pg/ml, (295±15) pg/ml, t=-9.41, P=0.000], IL-17 [(76 ±14) pg/ml, (99 ±16) pg/ml, t=-5.78, P<0.01], IL-23 [(85 ±9) pg/ml, (102 ±11 ( pg/ml, t=-11.71, P<0.01], TNF-α [(303 ±12) pg/ml, (345 ±17) pg/ml, t=-15.56, P=0.007], while Treg cells related cytokines TGF-β was significantly reduced [(42 ±7) ng/ml, (35 ±8) ng/ml, t=7.52, P=0.012]. Th17 cells related cytokines were significantly reduced including IL-1 [(93 ±10) pg/ml, (79 ±8) pg/ml, t=10.52, P<0.01], IL-6 [(245 ±11) pg/ml, (151 ±8) pg/ml, t=19.23, P<0.01], IL-17 [(76 ±10) pg/ml, (62 ±9) pg/ml, t=7.37, P=0.005], IL-23 [(84 ±11) pg/ml, (38 ±6) pg/ml, t=14.48, P=0.000], TNF-α [(294 ±8) ng/ml, (195 ±9) ng/ml, t=23.35, P<0.01], while Treg cells related cytokine TGF-β was significantly increased (41 ±8, 61 ±10, t=-10.61, P=0.000. Conclusion TCDD can increase Treg cells, reduce Th17 cells, so the Th17/Treg cell in RA patho-genesis could be re-balanced.