Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice

摘要

Homeostasis requires the immunologically silent clearance of apoptotic cells before they become pro-inflammatory necrotic cells. CD300f (CLM-1) is a phosphatidylserine receptor known to positively regulate efferocytosis by macrophages, and CD300f gene-deficient mice are predisposed to develop a lupus-like disease. Here we show that, in contrast to CD300f function in macrophages, its expression inhibits efferocytosis by DC, and its deficiency leads to enhanced antigen processing and T-cell priming by these DC. The consequences are the expansion of memory T cells and increased ANA levels in aged CD300f-deficient mice, which predispose CD300f-deficient mice to develop an overt autoimmune disease when exposed to an overload of apoptotic cells, or an exacerbated autoimmunity when combined with Fc gamma RIIB deficiency. Thus, our data demonstrates that CD300f helps to maintain immune homeostasis by promoting macrophage clearance of self-antigens, while conversely inhibiting DC uptake and presentation of self-antigens.