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.
Original language | English (US) |
---|---|
Pages (from-to) | 3450-3458 |
Number of pages | 9 |
Journal | European Journal of Immunology |
Volume | 38 |
Issue number | 12 |
DOIs | |
State | Published - 2008 |
Keywords
- Autoimmunity
- Cytokines
- T cells
- TNF
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy