title: APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 response.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Miami, Leonard Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Xiao
authors.forename: Seiichi
authors.initials: S
authors.lastname: Motomura
authors.forename: Eckhard R
authors.initials: ER
authors.lastname: Podack
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology; D049109:Cell Proliferation; D024043:Collagen Type II / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D024043:Collagen Type II; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D020381:Interleukin-17; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13