{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:14:02Z","timestamp":1785420842217,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,1]]},"group-title":"Immunology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["K01DK133670"],"award-info":[{"award-number":["K01DK133670"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HL166449"],"award-info":[{"award-number":["R01HL166449"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30AR073752"],"award-info":[{"award-number":["P30AR073752"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01DK128142"],"award-info":[{"award-number":["R01DK128142"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AI167285"],"award-info":[{"award-number":["R01AI167285"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01CA278197"],"award-info":[{"award-number":["R01CA278197"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/0599cs764","id-type":"ROR","asserted-by":"publisher"}]},{"name":"UCLA Goodman-Luskin Microbiome Center"},{"name":"Lawrence C. Pakula, MD IBD Education and Innovation Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Distinct host factors maintain intestinal homeostasis but are incompletely understood. The complement system is primarily liver-derived and serum-operative. However, there is growing recognition for complement-mediated host defense at mucosal surfaces. The alternative pathway, which is constitutively active at low levels and amplifies complement activation independent of antibodies, requires Complement Factor B (CFB). Despite its evolutionary conservation, the spatial, cellular, and functional roles of CFB in the intestine are poorly understood. Here, we show that CFB is produced in the human colon and is increased in patients with active inflammatory bowel disease. To isolate the role of local CFB in mucosal responses, we interrogated a mouse strain that has no circulating, liver-derived CFB but retains intact CFB expression in the gut. Global CFB-deficient mice succumb to colitis compared to these liver-specific knockout mice, suggesting that locally synthesized CFB mitigates colitis. Single-cell analyses identify enterocytes and fibroblasts as key CFB producers in the gut. Compartment-specific deletion of CFB from epithelial or stromal cells abrogates mucosal protection independent of circulating levels, which corroborates with pharmacological CFB inhibition. These findings redefine complement in the intestine as a locally regulated mucosal defense system and establish gut-derived CFB as a critical determinant of intestinal homeostasis.<\/jats:p>\n                <jats:sec>\n                  <jats:title>BRIEF SUMMARY<\/jats:title>\n                  <jats:p>The role of local immune mediators in gut mucosal immune responses is still not entirely understood. In this study, we demonstrate a novel role for complement protein Factor B, a key component of the alternative pathway, which is locally sourced through epithelial and stromal cells. In vivo modeling of impaired local Factor B synthesis results in worse colitis, revealing a key role for mucosal sourced components of the alternative pathway.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.31.697141","type":"posted-content","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T02:55:11Z","timestamp":1767322511000},"source":"Crossref","is-referenced-by-count":0,"title":["Mucosally sourced complement factor B modulates the host response to colitis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2851-2520","authenticated-orcid":false,"given":"Aayusha","family":"Thapa","sequence":"first","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1189-8547","authenticated-orcid":false,"given":"Aasritha","family":"Nallapu","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nnenna","family":"Mougboh","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9739-2236","authenticated-orcid":false,"given":"Swathi","family":"Nedunchezian","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushi","family":"Talati","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7073-3199","authenticated-orcid":false,"given":"Brian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6927-6177","authenticated-orcid":false,"given":"Jungheun","family":"Hyun","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7722-2638","authenticated-orcid":false,"given":"John Michael","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4821-1400","authenticated-orcid":false,"given":"Christopher S.","family":"Seet","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"},{"name":"Jonsson Comprehensive Cancer Center (JCCC), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0618-0869","authenticated-orcid":false,"given":"Hon Wai","family":"Koon","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-4310","authenticated-orcid":false,"given":"Zhaoping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA, USA"},{"name":"Center for Human Nutrition, David Geffen School of Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Department of Medicine, VA Greater Los Angeles HealthCare System, Los Angeles, CA 90073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7656-0982","authenticated-orcid":false,"given":"Matthew A.","family":"Ciorba","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4974-6992","authenticated-orcid":false,"given":"Kathrin","family":"Michelsen","sequence":"additional","affiliation":[{"name":"F. 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