{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DEFB103A, which encodes human β‐defensin 3 (hBD3), is a multifunctional antimicrobial peptide with a broad spectrum of activity against bacteria (including multidrug‐resistant strains), fungi, and other pathogens. hBD3 exhibits potent, salt‐insensitive microbicidal activity that is mediated in part by its ability to interact with lipid II and disrupt microbial cell wall biosynthesis, leading to membrane destabilization and cell lysis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its direct antimicrobial effects, hBD3 plays a significant immunomodulatory role. It is expressed predominantly by epithelial cells (e.g., skin, oral mucosa, lung) and can be induced by proinflammatory cytokines and bacterial stimuli (via Toll-like receptors), contributing to innate immune defenses against pathogens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, hBD3 is involved in recruiting immune cells; it acts as a chemoattractant by engaging receptors such as CCR2 and CCR6, and it promotes the expression of costimulatory molecules on monocytes and dendritic cells, thereby linking innate and adaptive immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural studies have revealed that hBD3 can form dimers and adopts a stable β‐sheet structure. Although the native disulfide bonds are not strictly necessary for its antimicrobial function, they are important for its chemotactic activity and receptor binding, underscoring a dual functional role for this peptide."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, hBD3’s capacity to modulate inflammatory responses is highlighted by its ability to dampen excessive proinflammatory cytokine production and NF-κB signaling under certain conditions, suggesting potential anti‐inflammatory as well as antimicrobial roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, DEFB103A/hBD3 serves as a critical effector molecule in the innate immune system. Its potent antimicrobial actions, combined with its role in immune cell recruitment and modulation of inflammatory signaling, make it an important component of epithelial defense mechanisms in diverse tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Harder, J Bartels, E Christophers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M008557200"}], "href": "https://doi.org/10.1074/jbc.M008557200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11085990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11085990"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Vera Sass, Tanja Schneider, Miriam Wilmes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human beta-defensin 3 inhibits cell wall biosynthesis in Staphylococci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Immun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/IAI.00688-09"}], "href": "https://doi.org/10.1128/IAI.00688-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20385753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20385753"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Heather R Conti, Fang Shen, Namrata Nayyar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20081463"}], "href": "https://doi.org/10.1084/jem.20081463"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19204111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19204111"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuping Lai, Anna L Cogen, Katherine A Radek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defense against bacterial skin infections."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2010.123"}], "href": "https://doi.org/10.1038/jid.2010.123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20463690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20463690"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Johann Röhrl, De Yang, Joost J Oppenheim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human beta-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0903984"}], "href": "https://doi.org/10.4049/jimmunol.0903984"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20483750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20483750"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhibin Wu, David M Hoover, De Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1533186100"}], "href": "https://doi.org/10.1073/pnas.1533186100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12840147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12840147"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "David J Schibli, Howard N Hunter, Vladimir Aseyev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The solution structures of the human beta-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M108830200"}], "href": "https://doi.org/10.1074/jbc.M108830200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11741980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11741980"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Fiona Semple, Sheila Webb, Hsin-Ni Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human beta-defensin 3 has immunosuppressive activity in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.200940041"}], "href": "https://doi.org/10.1002/eji.200940041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20104491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20104491"}]}]}]}