{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Intelectin‐2 (ITLN2) is emerging as a multifunctional lectin that contributes to innate mucosal immunity by recognizing microbial glycans, modulating cytokine‐driven inflammation, and potentially influencing mucus barrier properties. In parasitic infections, for example, ITLN2 is rapidly up‐regulated in the gastrointestinal epithelium of resistant mice and sheep challenged with nematodes (e.g."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " This up‐regulation is associated with early innate responses that may contribute to parasite expulsion and mucosal healing, consistent with its restricted expression in mucous neck or Paneth cells. "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of allergic airway inflammation, ITLN2 appears to mediate epithelial responses by facilitating interleukin‐13–induced chemokine production—thereby supporting the type 2 immune response—and its altered expression has been detected in experimental asthma models, highlighting its potential as a biomarker of airway disease"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, studies in sheep demonstrate that ITLN2 can associate with gastric mucins, suggesting that it may influence the biophysical properties of the mucus barrier and contribute to microbial defense."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In non‐mammalian models, such as zebrafish and rainbow trout, ITLN2 homologues have been shown to bind bacterial cell wall components and are among the most robustly expressed genes in stress‐responsive contexts, further supporting a conserved role in pathogen recognition and the innate immune response"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In humans, ITLN2 differs in primary structure and tissue localization from ITLN1, and its reduced expression in inflammatory bowel disease suggests that it may play a role in mucosal homeostasis and disease pathogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, ITLN2 has been implicated in other inflammatory contexts. In a viral encephalitis model, suppression of ITLN2 resulted in decreased nuclear factor‐κB activation and attenuated inflammation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and in studies of porcine immune function, enhanced ITLN2 expression in natural killer cells was observed following dietary supplementation with bovine lactoferrin, suggesting a role in modulating cellular immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Finally, ITLN2 expression is also responsive to radiation exposure, indicating that its transcriptional regulation may serve as a marker to distinguish dose‐dependent effects and radiation quality."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, the available data support a role for ITLN2 as an important mediator of mucosal innate defense mechanisms. Its rapid up‐regulation in response to parasitic and bacterial challenges and its involvement in modulating inflammatory and barrier functions underscore its potential as both a functional effector molecule in host defense and a biomarker in a range of disease states.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alan D Pemberton, Pamela A Knight, John Gamble, et al. 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