{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nILDR2, a type I transmembrane protein of the immunoglobulin superfamily, has been shown to play a pivotal immunomodulatory role. Its extracellular domain, when fused to an Fc fragment (ILDR2‐Fc), delivers potent inhibitory signals to T cells, thereby dampening inflammatory responses. This activity has translated into long‐term beneficial effects in animal models of autoimmune diseases such as experimental autoimmune encephalomyelitis and type 1 diabetes, and has even facilitated transplant engraftment through the induction of antigen‐specific regulatory T cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its well‐defined function in immune regulation, ILDR2 is expressed widely in nonlymphoid tissues, including the liver. Experimental modulation of hepatic ILDR2 levels has revealed its influence on lipid homeostasis and endoplasmic reticulum stress pathways. For instance, adenoviral knockdown of ILDR2 in murine livers was initially associated with steatosis, elevated triglycerides, and cholesterol accumulation, although subsequent data indicated that these alterations were likely due to off‐target effects rather than a direct role for ILDR2 in lipid metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, ILDR2 expression within stromal cells, such as fibroblastic reticular cells in lymph nodes, reinforces its broader immunoregulatory actions by influencing T cell recruitment and activation. Notably, disrupting its immunosuppressive signaling with a cross‐reactive anti‐ILDR2 antibody has emerged as a promising strategy in cancer immunotherapy, enhancing antigen‐specific T-cell proliferation and cytotoxicity, and showing synergistic efficacy when combined with agents like anti-PD-L1 or immunogenic chemotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joseph R Podojil, Iris Hecht, Ming-Yi Chiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ILDR2-Fc Is a Novel Regulator of Immune Homeostasis and Inducer of Antigen-Specific Immune Tolerance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1700326"}], "href": "https://doi.org/10.4049/jimmunol.1700326"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29431690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29431690"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Iris Hecht, Amir Toporik, Joseph R Podojil, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "ILDR2: an endoplasmic reticulum resident molecule mediating hepatic lipid homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0067234"}], "href": "https://doi.org/10.1371/journal.pone.0067234"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23826244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23826244"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Elizabeth J Millings, Maria Caterina De Rosa, Sarah Fleet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ILDR2 has a negligible role in hepatic steatosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0197548"}], "href": "https://doi.org/10.1371/journal.pone.0197548"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29847571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29847571"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Julia Huetter, Uwe Gritzan, Ilona Gutcher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of BAY 1905254, an Immune Checkpoint Inhibitor Targeting the Immunoglobulin-Like Domain Containing Receptor 2 (ILDR2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Immunol Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2326-6066.CIR-19-0321"}], "href": "https://doi.org/10.1158/2326-6066.CIR-19-0321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32312711"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32312711"}]}]}]}