{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCD93 is emerging as a multifunctional regulator of innate immunity. Studies in CD93‐deficient mice have shown that, although traditional in vitro phagocytic assays may appear largely unaltered, the in vivo clearance of apoptotic cells is impaired. This defect appears to be linked to dysregulated complement activation and abnormalities in leukocyte recruitment. Moreover, proteolytic shedding of membrane‐bound CD93—as well as the appearance of a soluble form—has been correlated with modulation of inflammatory processes and efficient engulfment of dying cells during tissue injury and immune challenge."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in innate responses, CD93 is critically involved in lymphohematopoiesis and B‐cell lineage maturation. Re‐expression of CD93 during plasma‐cell differentiation is essential for the maintenance of antibody secretion and the survival of long‐lived bone marrow plasma cells. Furthermore, early lymphohematopoietic progenitors that display CD93 (also known as AA4.1 in mice) demonstrate a bias toward lymphoid potential, and genetic polymorphisms in CD93 appear to influence early B‐cell developmental stages as well as susceptibility to autoimmune disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCD93 also plays a key role in vascular biology. In endothelial cells, it regulates integrin signaling and fibronectin fibrillogenesis—processes that are essential for vessel maturation, stabilization of cell–cell junctions, and angiogenic sprouting. In tumor models, the CD93–multimerin-2 interaction has been shown to guide the formation of endothelial filopodia and thereby supports proper vessel organization. Moreover, CD93 interaction with other endothelial regulators, including IGFBP7 and VEGFR2, ensures vascular integrity, limits aberrant permeability, and even modulates platelet function. These multifaceted actions establish CD93 as not only an angiogenic factor but also a guardian of the endothelial barrier in both physiological and pathological settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent insights have uncovered a role for CD93 in neural development. In the cerebral cortex, CD93 expressed by neural stem cells and neurons negatively regulates astrogenesis. Through interactions with extracellular matrix components such as multimerin-2 and subsequent modulation of β-catenin signaling, CD93 represses premature astrocyte differentiation; loss of this control leads to an increase in glial formation and has been associated with autism-like behavioral phenotypes in knockout models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, CD93 participates in metabolic regulation. In animal models of diet-induced metabolic stress, deficiency in CD93 has been linked to impaired glucose tolerance, reduced insulin sensitivity, and structural alterations in pancreatic islets. These findings suggest that, beyond its vascular and immune roles, CD93 may be an important mediator in maintaining glucometabolic homeostasis under conditions of nutritional stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Peter J Norsworthy, Liliane Fossati-Jimack, Josefina Cortes-Hernandez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "CD93 negatively regulates astrogenesis in response to MMRN2 through the transcriptional repressor ZFP503 in the developing brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1922713117"}], "href": "https://doi.org/10.1073/pnas.1922713117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32291340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32291340"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Rona J Strawbridge, Agneta Hilding, Angela Silveira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soluble CD93 Is Involved in Metabolic Dysregulation but Does Not Influence Carotid Intima-Media Thickness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db15-1333"}], "href": "https://doi.org/10.2337/db15-1333"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27659228"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27659228"}]}]}]}