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Article10.4049/jimmunol.190.supp.194.1

B7x modulates the adaptive immune response and diminishes renal injury in murine antibody mediated nephritis (P5168)

Rahul D. Pawar,Béatrice Goilav,Yumin Xia,Leal Herlitz,Kaya Ghosh,Xingxing Zang+1 more-2013-05-01-The Journal of Immunology
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Abstract B7x (B7-H4, B7S1), a member of the B7/CD28 co-stimulatory superfamily, is an inhibitor of T cell activation and proliferation. B7x is highly expressed in peripheral, non-lymphoid tissues. However, the in vivo function of B7x is largely unknown. We hypothesized that B7x may modulate the pathogenesis of antibody mediated nephritis through its effects on T cells. We induced nephritis in B7x-deficient (B7x-/-) (n=10) and B7x-wild type (WT) B6 mice (n=10) pre-immunized with rabbit IgG by intravenous injection of nephrotoxic sera (rabbit anti-mouse glomerular antibodies). Following nephritis induction we observed a significant increase in the levels of serum IgG, particularly of the IgG2b and IgG1 isotype, in B7x-/- mice as compared to B7x WT mice. At the mRNA level, IL-23, CCL2 and CCR5 were significantly upregulated in B7x-/- kidney tissue. Immunohistochemistry revealed significantly increased glomerular infiltration of CD3+ T cells and CD68+ macrophages in B7x-/- kidneys. Further

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Abstract B7x (B7-H4, B7S1), a member of the B7/CD28 co-stimulatory superfamily, is an inhibitor of T cell activation and proliferation. B7x is highly expressed in peripheral, non-lymphoid tissues. However, the in vivo function of B7x is largely unknown. We hypothesized that B7x may modulate the pathogenesis of antibody mediated nephritis through its effects on T cells. We induced nephritis in B7x-deficient (B7x-/-) (n=10) and B7x-wild type (WT) B6 mice (n=10) pre-immunized with rabbit IgG by intravenous injection of nephrotoxic sera (rabbit anti-mouse glomerular antibodies). Following nephritis induction we observed a significant increase in the levels of serum IgG, particularly of the IgG2b and IgG1 isotype, in B7x-/- mice as compared to B7x WT mice. At the mRNA level, IL-23, CCL2 and CCR5 were significantly upregulated in B7x-/- kidney tissue. Immunohistochemistry revealed significantly increased glomerular infiltration of CD3+ T cells and CD68+ macrophages in B7x-/- kidneys. Further

Keywords

NephritisImmune systemLupus nephritisAntibodyGlomerulonephritisPathogenesisGlomerular basement membraneImmunology

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