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Role of IL‐21R in the pathogenesis of murine models of SLE
Author(s) -
Andreyeva Tatyana A,
Guay Heath,
Damphousse Christie,
Bloom Laird,
Olland Stephane,
Brown Tom,
NickersonNutter Cheryl,
Collins Mary,
Young Debbie
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.1074.19
Subject(s) - antibody , immunology , systemic lupus erythematosus , immune system , cytokine , pathogenesis , b cell , immunoglobulin class switching , biology , autoimmune disease , medicine , disease
IL‐21 is a pleiotropic type I cytokine that is secreted by activated CD4 T cells. IL21 has been found to induce apoptosis in resting B cells but promotes class switch recombination and plasma cell differentiation of activated B cells. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a break down in both T and B cell tolerance, and the development of anti‐nuclear antibodies. Generation of high titers of IgG antibodies reactive with dsDNA coincides with disease progression. Thus, factors that promote B cell activation and antibody production, such as IL‐21, may be important for the development of SLE. We examined the role of IL‐21R in the cGVHD model of lupus‐like disease using IL‐21R deficient mice. Cells from bm12 mice were transferred into C57Bl/6 mice or into IL21R KO mice on the C57Bl/6 background to determine whether the lack of IL‐21R in the host would affect antibody production, immune complex deposition, and kidney pathology. All of these parameters were decreased in the IL21R KO recipient mice. We also show that treatment of MRL‐Faslpr mice with an antagonistic anti‐IL‐21R antibody significantly reduced anti‐dsDNA IgG serum antibody levels and prevented IC deposition and kidney pathology in these mice. Therefore, blockade of the IL‐21 pathway is a potential therapeutic target for the treatment of human lupus.