APRIL (TNFSF13) regulates collagen‐induced arthritis,IL‐17 production and Th2 response

A proliferation‐inducing ligand (APRIL or TNFSF13) shares receptors with B‐cell activation factor of the TNF family (BAFF) on B and T cells. Although much is known about the function of APRIL in B cells, its role in T cells remains unclear. Blocking both BAFF and APRIL suggested that BAFF and/or APRIL contributed to collagen‐induced arthritis (CIA); however, the role of APRIL alone in CIA remained unresolved. We show here that, in vitro, our newly generated APRIL^?/? mice exhibited increased T‐cell proliferation, enhanced Th2 cytokine production under non‐polarizing conditions, and augmented IL‐13 and IL‐17 production under Th2 polarizing conditions. Upon immunization with OVA and aluminum potassium sulfate, APRIL^?/? mice responded with an increased antigen‐specific IgG1 response. We also show that in APRIL^?/? mice, the incidence of CIA was significantly reduced compared with WT mice in parallel with diminished levels of antigen‐specific IgG2a autoantibody and IL‐17 production. Our data indicate that APRIL plays an important role in the regulation of cytokine production and that APRIL‐triggered signals contribute to arthritis. Blockade of APRIL thus may be a valuable adjunct in the treatment of rheumatoid arthritis.