{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nBTNL2 is a mucosa‐associated immunoregulatory molecule whose unique structural features—including two extracellular immunoglobulin‐like domains, a transmembrane region, and an unconventional cytoplasmic tail—underpin its role as a negative costimulator. Initial studies revealed that BTNL2 is predominantly expressed in digestive tract tissues, where its soluble form inhibits CD4⁺ T cell proliferation and cytokine production. Moreover, BTNL2 modulates the B7/CD28 signaling axis to promote Foxp3 expression, thereby favoring the induction of regulatory T cells that help maintain immune homeostasis under both asymptomatic and inflammatory conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, BTNL2 has emerged as a potent suppressor of antitumor immunity. Specifically, its engagement with local γδ T cell populations enhances IL-17A production within the tumor microenvironment, thereby limiting cytotoxic CD8⁺ T cell infiltration and facilitating tumor progression. Consistent with these findings, high levels of BTNL2 expression in human cancers correlate with poor overall patient survival. In parallel, the intricate molecular landscape in cancer also encompasses mechanisms such as multidrug resistance in breast cancer cells, highlighting the complex interplay of immunomodulatory and oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the intestinal milieu, BTNL2 further plays a critical role in fine-tuning the local immune response. It acts to restrict the homeostatic proliferation of tissue-resident γδ intraepithelial lymphocytes, thereby shaping their T cell receptor repertoire and regulating antimicrobial response modules. Disruption of BTNL2 signaling in the gut leads to altered γδ T cell specificities and exacerbated inflammation during colitis, underscoring its importance as a gatekeeper for intestinal immune balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Heather A Arnett, Sabine S Escobar, Eva Gonzalez-Suarez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BTNL2, a butyrophilin/B7-like molecule, is a negative costimulatory molecule modulated in intestinal 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.178.3.1523"}], "href": "https://doi.org/10.4049/jimmunol.178.3.1523"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17237401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17237401"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ryan M Swanson, Marc A Gavin, Sabine S Escobar, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Structural Insights into N-terminal IgV Domain of BTNL2, a T Cell Inhibitory Molecule, Suggests a Non-canonical Binding Interface for Its Putative Receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2020.09.013"}], "href": "https://doi.org/10.1016/j.jmb.2020.09.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32976909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32976909"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yanyun Du, Qianwen Peng, Du Cheng, et al. 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