{"type": "root", "children": [{"type": "t", "text": "<head>\n <meta charset=\"UTF-8\">\n <title>Summary of JAML Function</title>\n </head>\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Junctional adhesion molecule‐like protein (JAML) is an immunoglobulin‐superfamily member that plays multifaceted roles in regulating immune responses, tissue repair, and cell migration. Studies have demonstrated that in epithelial γδ T cells, JAML is expressed specifically on cells resident at barrier surfaces. Its binding to its major ligand—the coxsackievirus and adenovirus receptor (CAR)—provides potent costimulatory signals that trigger cellular proliferation as well as cytokine and growth factor production, thereby accelerating wound closure and tissue repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural analyses reveal that JAML’s unusual immunoglobulin‐domain assembly and charged interface underlie its specific interaction with CAR, which in turn facilitates the recruitment of phosphoinositide 3‐kinase (PI3K) to intracellular signaling motifs akin to those found on other costimulatory receptors such as CD28."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, JAML is expressed on various leukocyte populations including granulocytes. Its localization to regions of cell–cell contact suggests that it mediates homophilic interactions that enhance cell adhesion and transmigration—a process critical for leukocyte recruitment and extravasation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in mediating adhesive interactions, JAML has emerged as an important regulator within the tumor microenvironment. It supports the activation of both γδ tumor‐infiltrating lymphocytes (TILs) and CD8 T cells via engagement with CAR, thereby bolstering antitumor immunity—a function that can be harnessed therapeutically by agonistic anti‐JAML antibodies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, experimental models have identified JAML as a key mediator of transendothelial migration for mouse dendritic cells. In the human context, differential JAML expression has been linked with immune cell infiltration in lung adenocarcinoma, with lower levels correlating with poorer clinical outcomes, suggesting its potential as a prognostic biomarker in cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, JAML functions as a critical adhesion and costimulatory receptor that integrates extracellular binding events with intracellular signaling. This dual role is central not only to rapid immune cell activation and effective wound healing at epithelial barriers but also to the modulation of antitumor responses and cell migration across vascular and tissue interfaces.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Deborah A Witherden, Petra Verdino, Stephanie E Rieder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The junctional adhesion molecule JAML is a costimulatory receptor for epithelial gammadelta T cell activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1192698"}], "href": "https://doi.org/10.1126/science.1192698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20813954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20813954"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Petra Verdino, Deborah A Witherden, Wendy L Havran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The molecular interaction of CAR and JAML recruits the central cell signal transducer PI3K."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1187996"}], "href": "https://doi.org/10.1126/science.1187996"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20813955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20813955"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Christel Moog-Lutz, Florence Cavé-Riant, Florence C Guibal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JAML, a novel protein with characteristics of a junctional adhesion molecule, is induced during differentiation of myeloid leukemia cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2002-11-3462"}], "href": "https://doi.org/10.1182/blood-2002-11-3462"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12869515"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12869515"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Joseph M McGraw, Flavian Thelen, Eric N Hampton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JAML promotes CD8 and γδ T cell antitumor immunity and is a novel target for cancer immunotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20202644"}], "href": "https://doi.org/10.1084/jem.20202644"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34427588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34427588"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Seung-Eon Roh, Yideul Jeong, Myeong-Ho Kang, et al. 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