CD147 has also been linked to the regulation of T-cell development in thymus. In periphery, CD147 is expressed on activated lymphocytes especially activated regulatory T cells (Tregs) within the CD4+ FoxP3+ subset. We previously demonstrated deleterious effects of CD147 in renal inflammation caused by ischemia and renal fibrosis. As CD147 identifies activated human Tregs, the attention has become extended to the autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus. Interleukin
(IL)-17 producing T cell and Treg also serve important roles in the pathogenesis of SLE. However, the molecular mechanism involving CD147 remains unknown. We therefore investigated the role of CD147 in lupus nephritis. Methods: Lupus nephritis was induced see more in CD147 deficient mice (Bsg−/−) or wild-type mice (Bsg+/+) with an intraperitoneal injection of pristane (0.5 ml/each mice). They were sacrificed at 6 months after an injection for histological and biochemical analyses. Kidney, spleen and thymus were analyzed. Results: There was no difference between Bsg+/+ and Bsg−/− in
serum anti-nuclear/anti-dsDNA Belnacasan manufacturer antibody during the experimental period, whereas serum C3 decreased in Bsg−/−. Mesangial and endothelial cells proliferations, macrophages and CD4+ T cells infiltration, wire loop lesion and albuminuria were prominent in Bsg−/− mice. Consistent with these data, IgG, C3 and C1q depositions in Bsg−/− glomeruli were predominantly observed. By flow cytometry analysis, no obvious difference in the number of Treg was found in both genotypes, whereas IL-17A producing CD4+ T cells (Th17) were higher in Bsg−/− spleen than Bsg+/+. Th17-related gene expressions were prominent in Bsg−/− kidney. CD4+ T cells from Bsg−/− significantly
increased IL-17A level more than Bsg+/+ under Th17-skewing conditions. Interestingly, STAT3 activation, essential for Th17 differentiation, was enhanced by lack of CD147. Treatment with agonistic anti-CD147 antibody was downregulated the STAT3 activation. Conclusion: Lack of CD147 promotes Th17 differentiation through the STAT3 activation, eventually leading to the development of lupus nephritis. IKEUCHI HIDEKAZU, HIROMURA KEIJU, TSHILELA PDK4 KADIOMBO, A, KAYAKABE KEN, SAKURAI NORIYUKI, SAKAIRI TORU, KANEKO YORIAKI, MAESHIMA AKITO, NOJIMA YOSHIHISA Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine Introduction: Recently, we reported that multitarget therapy using tacrolimus (TAC) and mycophenolate mofetil (MMF) was effective in inducing early remission and in yielding a high remission rate in patients with active class III, IV, V lupus nephritis (LN) (Mod Rheumatol, 2013). Here, we conducted a follow-up study. Methods: All 16 patients in the previous study, 2 men and 14 women, 34.3 ± 8.