{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Loricrin is a major structural protein that is predominantly expressed during the late stages of keratinocyte differentiation in the epidermis. It constitutes a key component of the cornified envelope and is essential for assembling the robust, water‐impermeable barrier that protects the skin from external insults, dehydration, and pathogen invasion. In several inflammatory skin disorders—including atopic dermatitis and psoriasis—a marked reduction in loricrin expression contributes to barrier defects, facilitating increased penetration of allergens and microbes and thereby exacerbating inflammation. In these conditions, proinflammatory cytokines such as IL‑4, IL‑13, and TNF‑α are known to downregulate loricrin expression, further impairing the terminal differentiation process of keratinocytes and reducing the overall integrity of the epidermal barrier. Restoration of loricrin levels, as observed following therapeutic interventions that counteract these cytokines, reaffirms its crucial role in maintaining epidermal homeostasis. Collectively, these findings establish loricrin as a pivotal effector in the formation and maintenance of the skin barrier and underscore that its dysregulation is a critical factor in the pathogenesis of chronic skin inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Byung Eui Kim, Donald Y M Leung, Mark Boguniewicz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clim.2007.11.006"}], "href": "https://doi.org/10.1016/j.clim.2007.11.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18166499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18166499"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Byung Eui Kim, Michael D Howell, Emma Guttman-Yassky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TNF-α downregulates filaggrin and loricrin through c-Jun N-terminal kinase: role for TNF-α antagonists to improve skin barrier."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2011.24"}], "href": "https://doi.org/10.1038/jid.2011.24"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21346775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21346775"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Masutaka Furue "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms21155382"}], "href": "https://doi.org/10.3390/ijms21155382"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32751111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32751111"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kursad Turksen, Tammy-Claire Troy "}, {"type": "b", "children": [{"type": "t", "text": "Permeability barrier dysfunction in transgenic mice overexpressing claudin 6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.129.7.1775"}], "href": "https://doi.org/10.1242/dev.129.7.1775"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11923212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11923212"}]}]}]}