ICOS Controls Effector Function but Not Trafficking Receptor Expression of Kidney-Infiltrating Effector T Cells in Murine Lupus

摘要: Renal pathology in systemic lupus erythematosus involves both autoantibody deposition and a cellular inflammatory response, of which are mediated by effector CD4 T cells. MRLlpr mice spontaneously develop massive perivascular infiltrates, but the pathways that regulate development, trafficking, functions kidney-infiltrating cells poorly defined. To address these questions, we first surveyed chemokine protein levels nephritic kidneys from lupus-prone mice. After identifying highly elevated CXCR3 ligand CXCL9, found effectors enriched for expression CXCR3, as well P-selectin ICOS. Using genetic ablation, demonstrate ICOS plays an essential role establishment renal although small number infiltrating remain around blood vessels. Interestingly, though IgG production is substantially reduced Icos−/− mice, progression immune complex glomerulonephritis only modestly diminished chemokines, such remains high kidney. We find cell numbers slightly have normal with intact migration to CXCL9. However, they impaired cytokines fail show evidence efficient proliferation Thus, while dispensable acquisition trafficking receptor expression, strictly required local autoreactive murine lupus.