| Objective:With the widely application of HAART,the viral load of people living with HIV can be effectively controlled,but we still fail to eliminate the virus completely.The main difficulty in removing the virus is that the immune system in HIV-infected patients is dysfunctional such as the existence of exhausting state and can’t effectively remove the virus.How to improve cellular immune function in HIV patients and control the virus is a central issue that we have been focusing on.Given that miR-146 a plays an important role in diverse aspects of immune negative regulation,we would like to discuss the role of miR-146 a in immune exhaustion in patients with chronic HIV and its possible mechanism.Methods:Expressions of miR-146 a in PBMCs from 109 chronic HIV-1-infected patients with 35 gender-and age-matched HIV sero-negative healthy donors were determined by RT-qPCR.Then the expression of exhaustion markers as CTLA-4,TIM-3 and LAG-3 were also evaluated to analyze correlation between miR-146 a and these markers.We also tried to restore cellular immune function and reverse the exhaustion state by a blockage of miR-146 a in PBMCs in vitro.Results:The levels of miR-146 a in total PBMCs were significantly higher in chronic HIV-1-infected patients than in the control group(p < 0.01),and showed an inversecorrelation with CD4+ T-cell count.We also found exhaustion marker levels of CTLA-4,TIM-3 and LAG-3 in PBMCs from these patients were increased(P < 0.01),and positive correlated with the relative level of miR-146a(P < 0.05).While the levels of GZMB and perforin in patients’ PBMCs were lower.Moreover,overexpression of miR-146 a decreased antiviral cytokine production and inhibited the cytotoxicity of CD8+ T cells.Blockage of miR-146 a in PBMCs from chronic HIV infection exhibited an elevated antiviral cytokines production as well as the expression of GZMB and perforin,while simultaneously,decreased the inhibitory receptors expression,like PD-1,CTLA-4,TIM-3 and LAG-3.Conclusion:Elevated miR-146 a expression suppresses cellular immune function,and at least partially,contribute to immune exhaustion in HIV/AIDS patients.Therefore,miR-146 a might be considered as a predictor with potential to evaluate cellular immune function in AIDS. |
