{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T22:05:47Z","timestamp":1764194747852,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Plan Estatal de Investigacio\u0144 Cient\u0131f\u00edca y Te\u0107nica y de Innovacio\u0144, ISCIII. Subdirecci\u00f3n, General de Evaluaci\u00f3n y Fomento de la Investigacio\u0144, Ministerio de Econom\u00eda y Competitividad, Spain","doi-asserted-by":"publisher","award":["PI16\/01642","DK073339","AI-065687"],"award-info":[{"award-number":["PI16\/01642","DK073339","AI-065687"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["PI16\/01642","DK073339","AI-065687"],"award-info":[{"award-number":["PI16\/01642","DK073339","AI-065687"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ly108 (SLAMF6) is a homophilic cell surface molecule that binds SLAM-associated protein (SAP), an intracellular adapter protein that modulates humoral immune responses. Furthermore, Ly108 is crucial for the development of natural killer T (NKT) cells and CTL cytotoxicity. Significant attention has been paid towards expression and function of Ly108 since multiple isoforms were identified, i.e., Ly108-1, Ly108-2, Ly108-3, and Ly108-H1, some of which are differentially expressed in several mouse strains. Surprisingly, Ly108-H1 appeared to protect against disease in a congenic mouse model of Lupus. Here, we use cell lines to further define Ly108-H1 function in comparison with other isoforms. We show that Ly108-H1 inhibits IL-2 production while having little effect upon cell death. With a refined method, we could detect phosphorylation of Ly108-H1 and show that SAP binding is retained. We propose that Ly108-H1 may regulate signaling at two levels by retaining the capability to bind its extracellular as well as intracellular ligands, possibly inhibiting downstream pathways. In addition, we detected Ly108-3 in primary cells and show that this isoform is also differentially expressed between mouse strains. The presence of additional binding motifs and a non-synonymous SNP in Ly108-3 further extends the diversity between murine strains. This work highlights the importance of isoform awareness, as inherent homology can present a challenge when interpreting mRNA and protein expression data, especially as alternatively splicing potentially affects function.<\/jats:p>","DOI":"10.3390\/ijms24055024","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T04:29:58Z","timestamp":1678076998000},"page":"5024","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Ly108-H1 Signaling Reveals Ly108-3 Expression and Additional Strain-Specific Differences in Lupus Prone Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Svend","family":"Rietdijk","sequence":"first","affiliation":[{"name":"Unidad de Inmunolog\u00eda, IBIMER, CIBM, Universidad de Granada, 18016 Granada, Spain"},{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"},{"name":"Department of Gastroenterology and Hepatology, OLVG Hospital, 1091 AC Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marton","family":"Keszei","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilson","family":"Castro","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cox","family":"Terhorst","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3147-3535","authenticated-orcid":false,"given":"Ana C.","family":"Abad\u00eda-Molina","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda, IBIMER, CIBM, Universidad de Granada, 18016 Granada, Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular III e Inmunolog\u00eda, Facultad de Medicina, Universidad de Granada, 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.coi.2015.11.003","article-title":"SLAM Family Receptors in Normal Immunity and Immune Pathologies","volume":"38","author":"Wu","year":"2016","journal-title":"Curr. 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