In clinical practice, we found that microRNA (miR)-146a-5p is significantly up-regulated in peripheral blood mononuclear cells (PBMCs) of primary sjögren's syndrome (pSS) patients. In vitro experiments confirmed that miR-146a-5p promotes T helper 17 (Th17) cell differentiation, but the specific mechanism is still unknown. To solve this problem, 20 pSS patients and 20 healthy subjects were enrolled in this study and PBMCs were isolated from their blood. The expression of the membrane IL-23 R (mIL-23 R) in PBMCs was determined. CD3 + T cells were also isolated and used to further analyze the relationship between the ectodomain shedding of mIL-23 R and a disintegrin and metalloprotease 17 (ADAM17). Finally, miR-146a-5p inhibitor and mimics were transfected into PBMCs to evaluate the relationship between ADAM17 and mIL-23 R, and explore the role of mIL-23 R and ADAM17 in Th17 cell differentiation. Our results revealed a significantly increased expression of miR-146a-5p in PBMCs from pSS patients and significantly increased percentage of Th17 cells compared to PBMCs from healthy controls. Under polarization culture conditions, pSS patient-derived PBMCs can more easily differentiate into Th17 cells, which was, to a great extent, attributable to the increased expression of mIL-23 R. Moreover, ADAM17, an ectodomain sheddase of mIL-23 R, was targeted and negatively regulated by miR-146a-5p, which reduced the ectodomain shedding of mIL-23 R. Overall, our results suggested that miR-146a-5p could promote Th17 cell differentiation through targeting and negatively regulating ADAM17. Thus, these results might offer a new approach in the treatment of pSS.

IntroductionIdentifying the patients who are at risk for contrast-induced acute kidney injury (CI-AKI), which is defined as an increase in serum creatinine after exposure to contrast media, is a critical step in targeted prevention strategies. The absolute and relative importance of individual risk factors have not been systematically evaluated, let alone the new, controversial and modifiable risk factors of CI-AKI.Methods and analysisOn 1 July 2019, a search was performed on MEDLINE, Embase and the Cochrane Database of Systematic Reviews. We will perform a systematic review and meta-analysis to assess the important risk factors for developing CI-AKI, including those new, modifiable factors, which are considered controversial. The secondary endpoint will be all-cause mortality. Two authors will then independently screen studies that meet the criteria for inclusion, consulting with a third author to resolve any dispute. The quality of the included studies will be assessed according to the Newcastle-Ottawa scale.Ethics and disseminationEthics approval in this systematic review and meta-analysis protocol is not needed. We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.PROSPERO registration numberCRD42019121534