{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCD99-like 2 (CD99L2) is a widely expressed type I glycoprotein related to CD99 that is present on both endothelial cells and leukocytes. Initial studies demonstrated that CD99L2 mediates leukocyte transendothelial migration by promoting diapedesis—especially of neutrophils—through mechanisms that include homophilic interactions and facilitation of passage across the perivascular basement membrane. These findings, established by antibody blockade and adhesion assays in vitro, underscore a key role for CD99L2 in recruiting neutrophils and monocytes into sites of inflammation."}, {"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 tumor cell models, targeted downregulation of CD99L2 in murine B lymphoma (A20) cells resulted in altered morphology, decreased proliferation, prolonged cell cycle phases, and significant changes in cytokine profiles. These alterations—coupled with evidence of activated nuclear factor‐κB signaling—suggest that CD99L2 may also modulate tumor cell behavior and inflammatory signaling within neoplastic cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, in vivo studies employing conditional gene ablation of CD99L2 have confirmed its critical endothelial role in the inflammatory response. Genetic deletion of CD99L2 on endothelial cells impairs neutrophil and monocyte diapedesis in peritonitis models and limits leukocyte entry into the central nervous system during experimental autoimmune encephalomyelitis. These gene-targeting experiments highlight that the absence of endothelial CD99L2 reduces inflammatory cell infiltration—thereby alleviating tissue damage—without adversely impacting leukocyte adhesion or basal immune cell levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M Gabriele Bixel, Björn Petri, Alexander G Khandoga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A CD99-related antigen on endothelial cells mediates neutrophil but not lymphocyte extravasation in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-08-043109"}], "href": "https://doi.org/10.1182/blood-2006-08-043109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17344467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17344467"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alan R Schenkel, Eric M Dufour, Tina W Chew, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The murine CD99-related molecule CD99-like 2 (CD99L2) is an adhesion molecule involved in the inflammatory response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Commun Adhes (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15419060701755966"}], "href": "https://doi.org/10.1080/15419060701755966"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18163232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18163232"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ruth Seelige, Christiane Natsch, Sigrid März, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutting edge: Endothelial-specific gene ablation of CD99L2 impairs leukocyte extravasation in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1202721"}], "href": "https://doi.org/10.4049/jimmunol.1202721"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23293350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23293350"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fang Liu, Gong Zhang, Fanrong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of shRNA targeting mouse CD99L2 gene in a murine B cell lymphoma in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2013.2244"}], "href": "https://doi.org/10.3892/or.2013.2244"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23338758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23338758"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nakisha S Rutledge, Evan W Weber, Ryan Winger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD99-like 2 (CD99L2)-deficient mice are defective in the acute inflammatory response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Pathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexmp.2015.08.011"}], "href": "https://doi.org/10.1016/j.yexmp.2015.08.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26321243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26321243"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Maryna Samus, Ruth Seelige, Kerstin Schäfer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD99L2 deficiency inhibits leukocyte entry into the central nervous system and ameliorates neuroinflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/JLB.1A0617-228R"}], "href": "https://doi.org/10.1002/JLB.1A0617-228R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29791026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29791026"}]}]}]}