BAFF affects physiological T-cell activation through BAFF-R-mediated activation of the PI3K-Akt signaling pathway which mirrors one of the pathological mechanisms of T cell-mediated autoimmune diseases.
Although the BAFF receptor has been predicted to be the primary BAFF family receptor responsible for BAFF-driven humoral autoimmunity, in the current study we identify a critical role for signals downstream of Transmembrane Activator and CAML Interactor (TACI) in BAFF-dependent lupus nephritis.
Our findings reveal a previously undocumented, dose dependent, immunomodulatory distant effect resulting from BAFF receptor specific mAb-siRNA conjugate treatment in an in vivo model of autoimmune disease.
In mice, BAFF-R is required for B-cell maturation and survival, and in mice and humans, the overproduction of BAFF is associated with autoimmune disease.