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APRIL (TNFSF13) Promotes Collagen Induced Arthritis and IL‐17 Production and Inhibits IFN‐gamma and IL‐4 Production
Author(s) -
Xiao Yanping,
Motomura Seiichi,
Podack Eckhard R.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.663.24
Subject(s) - arthritis , immunology , medicine , t cell , pathogenesis , interleukin 17 , antibody , immune system , endocrinology
APRIL or TNFSF13 is a member of TNF super family. Analysis of APRIL knock out (APRIL−/−) mice gave conflicting results regarding B and T cell immunity. Therefore, we generated and characterized APRIL−/− mice and studied collagen induced arthritis (CIA). We confirmed that APRIL−/− mice have low basal IgA levels in serum. Splenic T cell proliferation was found increased in APRIL−/− mice. In the CIA model, the incidence of arthritis was decreased in APRIL−/− mice by about 35%, while disease severity and onset were unaffected. In mice with arthritis, chick and mouse anti‐collagen II specific IgG2a isotype antibody titers were significantly lower in APRIL−/− mice than in w.t. mice. Restimulated lymph node cells of w.t. CIA mice had elevated IL‐17 production which was diminished in APRIL−/− mice. The difference in IL‐17 production was disease specific and not observed upon restimulation of CD4 cells or in other disease models. However, APRIL−/− CD4 cells produced increased levels of IL‐4 and IFN‐? upon restimulation. Our data indicate that APRIL deficiency is responsible for diminished IgG2a levels and for diminished IL‐17 production which may be causally related to the pathogenesis of CIA. The combined effects of APRIL on antibody and IL‐17 may explain the decreased incidence of clinical arthritis in APRIL−/− mice. Our studies reveal an important role for APRIL in the regulation of Th1, Th2 and Th17 cytokines. This study is supported by AI 061807 and AI 068515.