{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:47:53Z","timestamp":1791244073968,"version":"4.1.0"},"reference-count":19,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health, Rome\u2014Italy","award":["#RC24\/2017"],"award-info":[{"award-number":["#RC24\/2017"]}]},{"name":"Ministry of Health, Rome\u2014Italy","award":["#RC08\/2021"],"award-info":[{"award-number":["#RC08\/2021"]}]},{"name":"Ministry of Health, Rome\u2014Italy","award":["#RC30\/2022"],"award-info":[{"award-number":["#RC30\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The B-cell adapter for PI3K (BCAP) is a protein that connects membrane receptor signaling to the PI3K pathway. In fibroblasts or dendritic cells, priming the cGAS nucleic-acid-sensing pathway increases BCAP expression and enhances type I interferon (IFN-I) production upon lipopolysaccharide (LPS) stimulation. These findings corroborate the idea that BCAP may bias cytokine production toward IFN during inflammation, indicating its potential involvement in IFN-driven diseases like systemic lupus erythematosus (SLE). We investigate the role of BCAP in regulating the inflammatory response in SLE and its relationship with IFN-mediated inflammation. BCAP gene expression and IFN signature were analyzed in 36 subjects with SLE and 20 healthy controls. Two cellular models were used to assess BCAP\u2019s role in LPS response and IFN signaling after cGAS stimulation. We found a correlation between BCAP and interferon-stimulated gene (ISG) expression in SLE. In a cellular model, tofacitinib and anifrolumab, acting as IFN signaling \u201cinhibitors\u201d, blocked BCAP overexpression triggered by cGAS, confirming BCAP as an ISG. Additional studies in BCAP\u2212\/\u2212 cells revealed that, in the absence of BCAP, these cells exhibited diminished IFN production upon LPS stimulation following prior exposure to cGAMP. Overall, BCAP is an ISG that acts as a positive regulator of Toll-like receptor 4-mediated IFN production. We speculate that its increased expression in SLE may contribute to a positive feedback loop, enhancing IFN production during bacterial infections.<\/jats:p>","DOI":"10.3390\/ijms26157034","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T08:45:18Z","timestamp":1753173918000},"page":"7034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["BCAP Is an Interferon-Stimulated Gene That Enhances Type I Interferon Activity in Response to Lipopolysaccharide"],"prefix":"10.3390","volume":"26","author":[{"given":"Marianna","family":"Di Rosa","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, University of Trieste, 34129 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia Maria","family":"Piperno","sequence":"additional","affiliation":[{"name":"Cellular Immunology, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-3794","authenticated-orcid":false,"given":"Alessandra","family":"Tesser","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0145-1976","authenticated-orcid":false,"given":"Alessia","family":"Pin","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Sospiro","sequence":"additional","affiliation":[{"name":"Cellular Immunology, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7380-8014","authenticated-orcid":false,"given":"Erica","family":"Valencic","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Boz","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Pastore","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6943-7927","authenticated-orcid":false,"given":"Alberto","family":"Tommasini","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Trieste, 34129 Trieste, Italy"},{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Benvenuti","sequence":"additional","affiliation":[{"name":"Cellular Immunology, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1182\/blood.V99.2.584","article-title":"Tyrosine phosphorylation of B-cell adaptor for phosphoinositide 3-kinase is required for Akt activation in response to CD19 engagement","volume":"99","author":"Inabe","year":"2002","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1073\/pnas.1118579109","article-title":"Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine\/threonine kinases PI3K\/Akt","volume":"109","author":"Troutman","year":"2012","journal-title":"Proc. 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