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Eur J Immunol. 2008 Dec;38(12):3450-8. doi: 10.1002/eji.200838640.

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

Author information

1
Department of Microbiology and Immunology, University of Miami, Leonard Miller School of Medicine, Miami, FL 33136, USA.

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.

PMID:
19016524
PMCID:
PMC2755626
DOI:
10.1002/eji.200838640
[Indexed for MEDLINE]
Free PMC Article

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