{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:16:06Z","timestamp":1791918966391,"version":"4.3.4"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"F. Widjaja Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>TNFSF8\/CD30 ligand is a TNF superfamily member expressed on several major immune cell types, including activated monocytes, B, and T cells. The signaling of CD30 ligand through its cognate CD30 receptor has been shown to have effects on cell differentiation, cell death\/survival, and cytokine production. The signaling pair has been implicated in hematopoietic malignancies and inflammatory disease, and a chemotherapy\u2013CD30 antibody combination for the treatment of Hodgkin and other lymphomas has been developed. There are two recorded isoforms of CD30 ligand. All hitherto studies of CD30 ligand are of the first, canonical isoform, while the second isoform has never been described. This study aims to elucidate the properties and signaling functions of the second CD30 ligand isoform. We have found mRNA expression of both isoforms in the PBMCs of all six healthy donors tested. Through methods in cell biology and biochemistry, we were able to discover that the second CD30 ligand isoform has no discernable pro-inflammatory function and, in fact, isoform 2 can restrict the capacity of the canonical isoform to signal through the CD30 receptor by preventing their interaction. This discovery has implications for the future development of therapeutics targeting the CD30\/CD30 ligand signaling pair in cancer and inflammatory disease.<\/jats:p>","DOI":"10.3390\/cimb46030172","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T11:37:22Z","timestamp":1711021042000},"page":"2741-2756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Opposite Functions of CD30 Ligand Isoforms"],"prefix":"10.3390","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7796-7373","authenticated-orcid":false,"given":"Ignat","family":"Printsev","sequence":"first","affiliation":[{"name":"F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyas","family":"Alalli","sequence":"additional","affiliation":[{"name":"F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6349-0957","authenticated-orcid":false,"given":"Janine","family":"Bilsborough","sequence":"additional","affiliation":[{"name":"F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/0092-8674(93)90361-S","article-title":"CD30 antigen, a marker for Hodgkin\u2019s lymphoma, is a receptor whose ligand defines an emerging family of cytokines with homology to TNF","volume":"73","author":"Smith","year":"1993","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e603","DOI":"10.1038\/bcj.2017.85","article-title":"Understanding CD30 biology and therapeutic targeting: A historical perspective providing insight into future directions","volume":"7","author":"Pileri","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1182\/blood.V83.8.2045.2045","article-title":"Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines","volume":"83","author":"Gruss","year":"1994","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1002\/jlb.63.6.752","article-title":"Construction and expression of a soluble form of human CD30 ligand with functional activity","volume":"63","author":"Powell","year":"1998","journal-title":"J. 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