Abrogation of autoimmune disease in Lyn-deficient mice by the deletion of IL-5 receptor alpha chain gene

Cellular Immunology
Byoung-gon MoonKiyoshi Takatsu

Abstract

Lyn, the src-family protein tyrosine kinase, plays a crucial role in the regulation of B cell antigen receptor (BCR)- and IL-5-receptor (IL-5R)-mediated signaling. Lyn-deficient mice have been reported to exhibit an increase in B-1 cell numbers, splenomegaly and accumulation of lymphoblast-like cells in the spleen with age, resulting in hyperimmunoglobulinemia and glomerulonephritis caused by the deposition of autoantibody complexes. To elucidate the role of IL-5 in B-1 cell activation, autoantibody production and autoimmune diseases, Lyn-deficient mice were crossed with IL-5Ralpha chain (IL-5Ralpha)-deficient mice and generated Lyn- and IL-5Ralpha-deficient (DKO) mice. In contrast to Lyn-deficient mice, DKO mice showed significantly reduced splenomegaly and lymphoadenopathy and reduced B-1 cell number in the peritoneal cavity. DKO mice also secreted low levels of IgM and IgG autoantibodies. Biochemical and histological analyses revealed that DKO mice showed milder pathogenesis of autoimmune-like disorders than Lyn-deficient mice. These results suggest involvement of IL-5 in enhanced B-1 cell activation, autoantibody production, and development of autoimmune disease in Lyn-deficient mice.

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Citations

Jun 28, 2006·Growth Factors·Margaret L Hibbs, Kenneth W Harder
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lixin RuiChristopher C Goodnow
Jul 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Evelyn TsantikosMargaret L Hibbs
Nov 22, 2012·European Journal of Immunology·Toni GutierrezAnne B Satterthwaite
Dec 8, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah A OrackiDavid M Tarlinton
Jul 29, 2021·Endocrinology·Ben F Brian, Tanya S Freedman

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