ELUCIDATION OF THE PATHOGENIC ROLE OF CD137 LIGAND IN A MURINE MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory condition. CD137 ligand (CD137L), via activating CD137 on T cells, is a potent driver of Tc/Th-1 responses. To investigate its involvement in the pathogenesis of SLE, B6.lpr-/-CD137L-/- double-knockout mice (DKO) were generated by crossing C57BL/6.Faslpr-/- (B6.lpr) lupus-prone mice and B6.CD137L-/- mice, which were compared phenotypically and immunologically, to B6.lpr and B6 WT mice. After a 22-month observation, DKO mice had significantly worse cutaneous lesions and glomerulonephritis, and higher mortality than their B6.lpr counterparts. DKO mice had a significantly higher proportion of Th17 cells than the B6.lpr mice. In vitro experiments revealed a significantly lower percentage of CD11b+ monocytes which were associated with lower intracellular IL-10 expression in the DKO than the B6.lpr mice. Additionally, DKO mice had significantly lower serum IL-10 levels than the B6.lpr mice. All these immunologic alterations are potentially responsible for more severe SLE after CD137L abrogation.