Th1 may play an important role in SLE progression
In vivo inflammation is induced by the immune complex, and if further activated, it can result in multiple organ injuries and promote the development of disease in SLE 43. A previous study reported that the levels of multiple cytokines in the serum were increased in MRL/lpr mice 44, and researchers also believe that the polarization of T cells in SLE involves changes from Th1 to Th2 cells and that IFN-α promotes the differentiation of activated B cells into plasma cells, thus playing an essential role in the progression of disease 45, 46. Recently, detailed research has begun to reveal the important role that IFN-γ plays in the development of lupus in MRL/lpr mice 44, 47-49.
Firstly, serum IFN-γ levels have been found to be significantly higher in both SLE patients and SLE murine models 44, 47. IFN-γ has been demonstrated to dramatically promote the proliferation and accumulation of DN T cells and to significantly increase the expression of FasL on the surfaces of DN T cells in lupus mice48, 49. Simultaneously, the accumulation of plasma cells is regarded to be a cardinal character in SLE 12, 21-23. Meanwhile, researchers have recently identified that the majority of accumulated plasma cells are expressed in the T cell marker CD3 and that the majority of these CD138+ T cells are also DN T cells12, 14. These findings suggest that these abnormal T cells may play a more important role in SLE, but not only in B cells.
Previous studies have also shown that the frequency of Th1 cells in Fas-deficient lupus mice are significantly higher in vivo , but this is not true for Th2 12, 50. Evidence suggests that IFN-γ-/- lpr mice exhibit significantly relieved symptoms of lupus, compared with IFN-γ+/+ lpr mice 48. IFN-RII deficiency has been suggested to significantly protect MRL/lpr mice from the development of significant autoimmune associated lymphadenopathy, autoantibodies, and renal disease, compared with IFN-RI deficiency in MRL/lpr mice 51, 52. These results indicate that IFN-γ and Th1 cells may be involved in the mechanisms of lupus development and tissue injuries in MRL/lpr mice. Recent research has even proposed that IFN-γ is required for the TLR7-promoted development of autoreactive B cells 51.