{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CD46, also known as membrane cofactor protein (MCP), is a widely expressed transmembrane regulator that plays multiple roles in immune homeostasis. It functions as a key complement regulator by acting as a cofactor for factor I–mediated cleavage of C3b and C4b, thereby protecting host cells from excessive complement activation—a role highlighted by studies in atypical hemolytic uremic syndrome (aHUS), where mutations in CD46 predispose to disease yet are associated with a relatively favorable prognosis compared with other complement defects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its complement regulatory functions, CD46 serves as an important costimulatory molecule in T cells. Engagement of CD46 together with the T cell receptor and interleukin‑2 induces the differentiation of IL‑10–producing regulatory (Tr1) cells and promotes the expression of granzyme B, thereby modulating effector functions and contributing to the fine tuning of adaptive immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CD46 also functions as a cellular receptor for several viral pathogens. It mediates attachment and entry of certain adenovirus serotypes—including species B adenoviruses such as Ad11 and Ad3—which exploit CD46 to gain access to host cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, the protective properties of CD46 have been harnessed therapeutically; for example, transgenic expression of human CD46 on porcine islets has been shown to limit complement‐mediated injury and improve graft survival in xenotransplantation models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these studies underscore the multifunctional nature of CD46 as both a guardian against complement‐mediated damage and a modulator of T cell activation, as well as its exploitation by pathogens and its potential in clinical applications.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marina Noris, Jessica Caprioli, Elena Bresin, et al. 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