{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:05:30Z","timestamp":1793502330423,"version":"4.5.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    IL-23 is implicated in the pathogenesis of immune-mediated inflammatory diseases, and myeloid cells that express Fc gamma receptor 1 (Fc\u03b3RI or CD64) on their surface have been recently identified as a primary source of IL-23 in inflamed tissue. Our complementary analyses of transcriptomic datasets from psoriasis and IBD showed increased expression of CD64 and IL-23 transcripts in inflamed tissue, and greater abundance of cell types with co-expression of CD64 and IL-23. These findings led us to explore potential implications of CD64 binding on the function of IL-23\u2013targeting monoclonal antibodies (mAbs). Guselkumab and risankizumab are mAbs that target the IL-23p19 subunit. Guselkumab has a native Fc domain while risankizumab contains mutations that diminish binding to Fc\u03b3Rs. In flow cytometry assays, guselkumab, but not risankizumab, showed Fc-mediated binding to CD64 on IFN\u03b3-primed monocytes. Guselkumab bound CD64 on IL-23\u2013producing inflammatory monocytes and simultaneously captured IL-23 secreted from these cells. Guselkumab binding to CD64 did not induce cytokine production. In live-cell confocal imaging of CD64\n                    <jats:sup>+<\/jats:sup>\n                    macrophages, guselkumab, but not risankizumab, mediated IL-23 internalization to low-pH intracellular compartments. Guselkumab and risankizumab demonstrated similar potency for inhibition of IL-23 signaling in cellular assays with exogenous addition of IL-23. However, in a co-culture of IL-23\u2013producing CD64\n                    <jats:sup>+<\/jats:sup>\n                    THP-1 cells with an IL-23\u2013responsive reporter cell line, guselkumab demonstrated Fc-dependent enhanced potency compared to risankizumab for inhibiting IL-23 signaling. These\n                    <jats:italic>in vitro<\/jats:italic>\n                    data highlight the potential for guselkumab binding to CD64 in inflamed tissue to contribute to the potent neutralization of IL-23 at its cellular source.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1532852","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:03:31Z","timestamp":1741752211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["Guselkumab binding to CD64+ IL-23\u2013producing myeloid cells enhances potency for neutralizing IL-23 signaling"],"prefix":"10.3389","volume":"16","author":[{"given":"Kacey L.","family":"Sachen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Hammaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indra","family":"Sarabia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Stoveken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hartman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin L.","family":"Leppard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Manieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuc","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Greving","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eilyn R.","family":"Lacy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"DuPrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Wertheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janise D.","family":"Deming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He (Hurley)","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom C.","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brice","family":"Keyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Kohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Karpowich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Steele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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