Endogenous CD100 promotes glomerular injury and macrophage recruitment in experimental crescentic glomerulonephritis

M Li, KM O'Sullivan, LK Jones, C Lo, T Semple… - …, 2009 - Wiley Online Library
M Li, KM O'Sullivan, LK Jones, C Lo, T Semple, A Kumanogoh, H Kikutani, SR Holdsworth…
Immunology, 2009Wiley Online Library
CD100 participates in adaptive immune responses and is important in neural cell migration.
To determine the role of endogenous CD100 in severe glomerular inflammation, we induced
experimental crescentic glomerulonephritis by planting a foreign antigen in glomeruli of
sensitized normal and CD100‐deficient (CD100−/−) mice. Fewer CD100−/− glomeruli
exhibited crescent formation or severe histological changes. Antigen‐specific immune
responses were reduced in CD100−/− mice. There was less interferon (IFN)‐γ and …
Summary
CD100 participates in adaptive immune responses and is important in neural cell migration. To determine the role of endogenous CD100 in severe glomerular inflammation, we induced experimental crescentic glomerulonephritis by planting a foreign antigen in glomeruli of sensitized normal and CD100‐deficient (CD100−/−) mice. Fewer CD100−/− glomeruli exhibited crescent formation or severe histological changes. Antigen‐specific immune responses were reduced in CD100−/− mice. There was less interferon (IFN)‐γ and interleukin (IL)‐4 production by splenocytes and fewer activated T and B cells were present in lymph nodes of immunized CD100−/− mice. Serum antigen‐specific immunoglobulin (IgG) levels were also decreased. Glomerular macrophage and CD4+ cell infiltration, and IgG and C3 deposition were attenuated. Normal kidneys expressed mRNA for CD100 and plexin‐B1 (the tissue receptor of CD100). Direct immunofluorescence showed that renal‐CD100 protein was predominantly in tubules, while plexin‐B1 was present in both glomeruli and tubules. To determine whether glomerular plexin‐B1 mediates leucocyte recruitment via leucocyte CD100, recruitment was studied after passive transfer of heterologous antibody (attracting neutrophils) or isologous antibody (attracting macrophages). Glomerular macrophages were reduced in CD100−/− mice, but neutrophil recruitment was equivalent, consistent with CD100 expression on macrophages, but not neutrophils. CD100 promotes severe nephritogenic immune responses and leucocyte CD100–glomerular plexin‐B1 interactions enhance macrophage recruitment to glomeruli.
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