{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough the provided abstracts do not specifically mention SNORD113‐3, they collectively describe the multifaceted roles of airway secretory proteins—primarily SPLUNC1 (short palate, lung, and nasal epithelium clone 1) and its related family members such as BPIFA1—in pulmonary host defense. These studies demonstrate that SPLUNC1 and BPIFA1 are secreted by the respiratory epithelium where they exert direct antimicrobial and antiviral effects. They inhibit the growth of bacteria (for example, Mycoplasma pneumoniae, Klebsiella pneumoniae, and Burkholderia cenocepacia), prevent bacterial biofilm formation by modulating airway surface tension, and even restrict viral entry, thereby reducing the overall pathogen burden in the lungs. In addition, these proteins are upregulated via pathogen‐recognition receptors (e.g., TLR2) to mount an immediate defense response, while simultaneously modulating neutrophil activity and cytokine production to fine‐tune the immune response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n \nIn addition to these direct antimicrobial actions, the studies highlight an important immunomodulatory role for these epithelial proteins under both infectious and allergic conditions. Reduced expression of SPLUNC1 in the context of a Th2 cytokine milieu or allergic inflammation is associated with impaired bacterial clearance, enhanced recruitment of inflammatory cells (including eosinophils and myeloid-derived suppressor cells), and increased airway hyperresponsiveness. For example, diminished levels lead to defects in neutrophil activation and elastase activity, thereby exacerbating lung injury and contributing to chronic airway diseases such as asthma and otitis media."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": "\n \nDetailed tissue localization studies further underscore that these secreted proteins are predominantly expressed within the nasal passages, upper airways, and submucosal glands—sites that serve as the first line of defense against inhaled pathogens. Their regulated expression under both pathogen challenge and inflammatory stimuli, as well as their interactions with other membrane components (such as the epithelial sodium channel in cystic fibrosis), not only contribute to effective microbial clearance but also may play roles in tumor suppression and the maintenance of overall airway homeostasis. Notably, other protective agents such as CC16 are emerging as complementary mediators in the lung’s innate immune repertoire."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "E E LeClair, V Nomellini, M Bahena, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and expression of a mouse member of the PLUNC protein family exclusively expressed in tongue epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygeno.2003.09.015"}], "href": "https://doi.org/10.1016/j.ygeno.2003.09.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15028288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15028288"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hong Wei Chu, Jyoti Thaikoottathil, John G Rino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Function and regulation of SPLUNC1 protein in Mycoplasma infection and allergic inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.179.6.3995"}], "href": "https://doi.org/10.4049/jimmunol.179.6.3995"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17785838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17785838"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hong Wei Chu, Fabienne Gally, Jyoti Thaikoottathil, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "SPLUNC1/BPIFA1 contributes to pulmonary host defense against Klebsiella pneumoniae respiratory infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2013.01.050"}], "href": "https://doi.org/10.1016/j.ajpath.2013.01.050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23499554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23499554"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Clemente J Britto, Qing Liu, David R Curran, et al. 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