Apoptosis-induced loss of CD43 from T cells promotes efferocytosis

The rapid and efficient phagocytic clearance of apoptotic cells by efferocytosis is a critical process for maintaining tissue homeostasis and immune function. T cells undergo apoptosis during thymic education and in the periphery, and require rapid clearance. CD43 is a bulky and heavily-glycosylated transmembrane protein highly expressed on the T cell surface. The function of CD43 in immune responses is mostly attributed to its anti-adhesive properties that negatively regulate cell-cell interactions. However, how CD43 might be modulated during cell apoptosis and whether such potential modulation might influence efferocytosis are not known. In this study, I demonstrate that CD43 is promptly and selectively eliminated from the human T cell surface during apoptosis, and the removal is mediated by the ADAM10 sheddase, whose activation is associated with surface-exposed phosphatidylserine that flips from the inner to outer leaflet of the plasma membrane. I established a novel efferocytosis assay and used this to show that CD43 removal increases the uptake of apoptotic T cells in an ADAM10-regulated manner. These findings present a novel regulatory pathway for CD43 expression and reveal CD43 as a ‘don’t eat me’ barrier for efferocytosis with implications for developing therapeutic strategies against pathological conditions that are associated with efferocytosis.