The Role of PD-1/PD-Ls in the Pathogenesis of IgG4-RD.

OBJECTIVE To investigate the role of Programmed cell death protein 1 (PD-1) and its two ligands PD-L1 and PD-L2 in the pathogenesis of IgG4-RD. METHODS Patients with IgG4-RD (n = 43) as well as healthy controls (n = 34) were recruited. Expression levels of PD-1, PD-L1 and PD-L2 in plasma, submandibular gland and T cell subsets were determined by ELISA, immunohistochemistry and flow cytometry. Naive T cells were stimulated with or without PD-L1/PD-L2 or anti-PD-L1/anti-PD-L2 for 7 days and the proportion of CD4+CD25+Treg cells was detected by flow cytometry. RESULTS The expression of PD-1, PD-L1 and PD-L2 in the plasma, submandibular gland and on the surface of Treg cells were increased in IgG4-RD patients. Plasma sPD-1 was positively correlated with serum IgG, IgG1, IgG3, IgG4, IgG4-RD RI and numbers of organs involved, and negatively correlated with serum IgM, IgA, C3 and C4. Plasma sPD-L2 was positively correlated with serum IgG1, plasma sPD-L1 was positively correlated with sPD-L2 and negatively correlated with C3. Stimulation of PD-L1 but not PD-L2 promoted the differentiation of naive T cells from IgG4-RD patients into CD4+CD25+Treg cells. CONCLUSION Plasma concentration of sPD-1, sPD-L1 and sPD-L2 were significantly increased in patients with IgG4-RD, and the expression of PD-1 and PD-L2 on Treg cells were upregulated. PD-1/PD-L1 can promote the differentiation of naive T cells into Treg cells and thus participate in the pathogenesis of IgG4-RD.