Arl8b and its role in the development of systemic lupus erythematosus by regulating T-cell number.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. Various factors contribute to its onset, and research has examined these diverse causes. Toll-like receptor (TLR) 7 has been suggested in many reports to be involved in the development of SLE, but much about its development remains unclear. We previously reported that ADP-ribosylation factor-like 8b (Arl8b), a small GTPase associated with TLR7, is involved in the production of type I interferon (IFN-Ⅰ) via TLR7, and that Arl8b is involved in the development of SLE in BXSB.Yaa, a TLR7-dependent SLE model mouse. This time, to determine whether Arl8b is involved in the pathogenesis of SLE in a manner largely independent of TLR7, we generated Arl8b-deficient MRL/lpr mice using the MRL/lpr mouse model, which exhibits low TLR7 dependency. The onset of SLE was found to be delayed. Splenomegaly and lymphadenopathy were reduced, and although T-cell activation was unaffected, the abnormal increase in T-cell numbers was markedly reduced. Furthermore, the age-related decline in the proportion of regulatory T cells (Tregs) was also suppressed. Arl8b was thus clearly demonstrated to be involved in the development of SLE in various ways. Arl8b, which is involved in regulating the immune system in this way, may be a promising target molecule for the treatment of SLE.