{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTHRIL (TNFα and hnRNPL related immunoregulatory lincRNA) was first identified as an essential long intergenic non‐coding RNA that regulates innate immune responses. In macrophages, THRIL (formerly linc1992) forms a complex with hnRNPL to bind the TNFα promoter, thereby promoting the transcription of TNFα and modulating the expression of other immune‐responsive genes. Its expression level is closely associated with the severity of inflammatory diseases, as first demonstrated in Kawasaki disease patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSubsequent investigations have expanded the functional spectrum of THRIL in various inflammatory and cardiovascular contexts. Increased THRIL expression has been correlated with acute respiratory distress syndrome risk in sepsis, and its dysregulation has been linked to coronary heart disease and pediatric immune thrombocytopenia, highlighting its relevance in modulating inflammatory cytokine milieu in these disorders. In coronary atherosclerotic heart disease, THRIL exerts part of its effect by regulating the AKT signaling pathway and directly interacting with proteins such as FUS, while in macrophages, depletion of THRIL not only dampens proinflammatory cytokine production but also enhances cholesterol efflux, partly via interactions with FOXO1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTHRIL has also been implicated in respiratory and systemic inflammatory conditions. Elevated THRIL levels have been observed in COVID-19 patients, where its modulation appears to track with the inflammatory phase of the disease. Moreover, by targeting specific microRNAs (miR‑34a and miR‑125b), THRIL influences immune regulation in allergic rhinitis and childhood asthma, and its altered expression profiles are evident in inflammatory bowel disease as well as pulmonary tuberculosis. Collectively, these studies underscore THRIL’s multifaceted role as an immune-regulatory lncRNA whose aberrant expression is linked to heightened inflammation and disease severity across a spectrum of pathological conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhonghan Li, Ti-Chun Chao, Kung-Yen Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1313768111"}], "href": "https://doi.org/10.1073/pnas.1313768111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24371310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24371310"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yan'e Wang, Xiaoxing Fu, Bo Yu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA THRIL promotes foam cell formation and inflammation in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbin.11934"}], "href": "https://doi.org/10.1002/cbin.11934"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36229925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36229925"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mohammad Abbasi-Kolli, Javid Sadri Nahand, Seyed Jalal Kiani, et al. 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