{"type": "root", "children": [{"type": "t", "text": "<div>\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CD14 is a multifunctional pattern recognition receptor that plays a central role in innate immunity by binding and trafficking acylated microbial products such as lipopolysaccharide (LPS) to Toll‐like receptor (TLR) signaling complexes. Structural studies reveal that human CD14 possesses an amino‐terminal pocket designed to accommodate lipid ligands, enabling the initiation of proinflammatory cascades that can be both protective and pathologic."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the central nervous system and peripheral tissues, CD14 modulates diverse disease processes. For instance, its participation in neuroimmune signaling has been linked to regulation of alcohol consumption and neuropathic pain, as loss of CD14 attenuates LPS/TLR4‐mediated nociceptive responses, while soluble CD14 derived from microglia may act to counterbalance excessive glial activation in neurodegenerative diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer biology, CD14 expression can delineate functionally distinct cell populations, with high CD14 levels in bladder and colorectal cancer cells correlating with increased production of inflammatory mediators, recruitment of immunosuppressive myeloid cells, and ultimately, enhanced tumor growth and poor clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Conversely, genetic variations in the CD14 promoter have been associated with differential immune responses in conditions such as asthma, altered IgE production, and metabolic dysregulation, underscoring its influence on susceptibility to inflammatory and metabolic diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, CD14 is critical for effective TLR4-mediated responses to both exogenous (e.g., bacterial endotoxins, scorpion venom, and viral components) and endogenous ligands, serving as a co-receptor that not only amplifies inflammatory signaling through its interactions with various ligands and adaptor molecules but also regulates receptor internalization to modulate subsequent cellular responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": " Synthetic antagonists that target CD14 further underscore its therapeutic potential by competitively inhibiting ligand binding and attenuating downstream TLR4 activation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", while antibody-mediated ligation of CD14 can induce receptor internalization and modulate cellular sensitivity to LPS."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In inflammatory conditions beyond infection, CD14-dependent signaling has been shown to contribute to the pathogenesis of ventilator-induced lung injury through interactions with endogenous ligands such as WISP1, and is a pivotal mediator in experimental cerebral malaria where its absence reduces disease severity and parasitemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Additionally, studies of apoptotic cell clearance have identified a critical role for CD14—specifically residue 11—in tethering dying cells to macrophages, a function that is extended to non-professional phagocytes in various tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, CD14 is integral to the modulation of immune cell activation, as exemplified by its requirement in lectin-induced macrophage responses wherein CD14 collaborates with TLR2 to trigger a robust proinflammatory and antimicrobial program."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " CD14’s diverse roles, spanning microbial recognition, signal amplification, receptor internalization, and immunomodulation, underpin its importance as both a biomarker and a potential therapeutic target across a range of inflammatory, infectious, and neoplastic diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n</div>"}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuri A Blednov, Igor Ponomarev, Chelsea Geil, et al. 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