Blockade of Th17 response by IL-38 in primary Sjogren's syndrome

Background: T helper 17 (Th17) cell responses were involved in the pathophysiology of primary Sjogren's syndrome (pSS). IL-38 has been reported to inhibit the secretion of chemokines involved in Th17 pathway. This study aimed to explore the regulation of Th17 response by IL-38 in pSS. Methods: Twenty-four pSS patients, 15 non-pSS control, and 13 health subjects were recruited. The expression of IL-38 and Th17 cytokines were detected and compared between pSS and controls. Human peripheral blood mononuclear cells (PBMCs) and minor salivary gland mononuclear cells (MSGMs) were purified and stimulated by IL-38. The differentiation and function of Th17 cells were evaluated by PCR and enzyme-linked immunosorbent assay (ELISA). Results: The pSS patients presented with significantly lower expression of IL-38 and higher Th17 cytokines (IL-17 and IL-23) compared with both non-pSS and healthy controls. The IL-38 inhibited the differentiation and function of Th17 responses from PBMCs and MSGMs. The IL-38 treatment could inhibit the Th17 response in mice model. Conclusions: IL-38 inhibits T helper 17 type responses in pSS, suggesting that IL-38 may be used as potential treatment target in pSS.