{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The human defensin beta‐4A (DEFB4A), which encodes the inducible antimicrobial peptide commonly known as human beta‐defensin 2 (hBD‐2), plays a central role in linking innate and adaptive immunity at epithelial surfaces. DEFB4A is expressed and further upregulated by epithelial and innate immune cells in response to microbial products and proinflammatory cues – including interleukin‐17, interleukin‐22, tumor necrosis factor‐α, and IL‐1β – via pathways that involve Toll‐like receptor signaling and vitamin D receptor activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Its expression can be synergistically induced by the cytokines released from Th17 cells and other innate signal–operating pathways, resulting in enhanced production of hBD‐2 by keratinocytes, airway epithelial cells, and other barrier cells. This rapid boost in DEFB4A expression contributes not only to direct antimicrobial actions against a broad spectrum of pathogens—including Gram‐negative bacteria, mycobacteria, and other opportunistic organisms—but also to the chemotaxis and activation of immune cells that help to orchestrate local inflammatory and wound‐healing responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, genetic factors such as variation in genomic copy number at the beta‐defensin locus (which includes DEFB4A) have been implicated in disease susceptibility—for example, lower gene copy numbers are associated with an increased risk of inflammatory disorders like colonic Crohn disease and psoriasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, DEFB4A functions as a key effector molecule of the innate immune defense by providing direct antimicrobial activity and modulating inflammatory responses. Its regulated expression through multiple convergent signaling pathways ensures that epithelial barriers can rapidly respond to microbial challenges while also influencing the recruitment and activation of immune cells. This multifaceted role makes DEFB4A an important mediator in host defense and inflammation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Spencer C Liang, Xiang-Yang Tan, Deborah P Luxenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20061308"}], "href": "https://doi.org/10.1084/jem.20061308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16982811"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16982811"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Philip T Liu, Mirjam Schenk, Valencia P Walker, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Vitamin D induces interleukin-1β expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1003407"}], "href": "https://doi.org/10.1371/journal.ppat.1003407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23762029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23762029"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Klaus Fellermann, Daniel E Stange, Elke Schaeffeler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/505915"}], "href": "https://doi.org/10.1086/505915"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16909382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16909382"}]}]}]}