Adp-Ribosylation Factor-Like 8b Is Required For The Development Of Mouse Models Of Systemic Lupus Erythematosus

Toll-like receptor 7 (TLR7) and type I interferons (IFN-1) are essential for the development of systemic lupus erythematosus (SLE) models such as BXSB.Yaa and 2,6,10,14-tetramethyl-pentadecane (TMPD)-induced experimental lupus. However, the mechanism underlying the development of SLE remains undefined. We report a requirement for ADP-ribosylation factor-like 8b (Arl8b) for TLR7-dependent IFN-1 production in plasmacytoid dendritic cells (pDCs). We analyzed whether Arl8b plays a role in two SLE models by comparing wild-type and Arl8b-deficient Arl8b GeneTrap (Arl8b(Gt/Gt)) mice. We found that BXSB.Yaa Arl8b(Gt/Gt) mice showed none of the abnormalities characterized in BXSB.Yaa mice. TMPD treatment of Arl8b(Gt/Gt) mice significantly inhibited the development of SLE. pDCs were required for TMPD-induced peritonitis. Our data demonstrate that Arl8b contributes to disease pathogenesis in two SLE models via IFN-1-dependent and -independent mechanisms and suggest that Arl8b is an attractive new target for therapeutic intervention in SLE.Arl8b is essential for SLE development