{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:15:46Z","timestamp":1785413746546,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["P01AI179405"],"award-info":[{"award-number":["P01AI179405"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"award":["P01AI179405"],"award-info":[{"award-number":["P01AI179405"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Health Region South-East","award":["2023015"],"award-info":[{"award-number":["2023015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Current treatment of lupus nephritis (LN) relies on broad immunosuppression and often fails to eradicate intrarenal immune niches that sustain inflammation. Tertiary lymphoid structures (TLS)\u2014organized aggregates of immune cells forming in chronically inflamed non-lymphoid tissues\u2014are increasingly recognized as drivers of local immune activation and tissue injury in LN. We previously showed that genetic CaMK4 deficiency suppresses autoimmunity and nephritis in lupus-prone mice. Here, we tested whether CaMK4 regulates renal TLS-like organization. Using kidneys from MRL\/lpr mice that were CaMK4-deficient or treated with KN93-loaded nanoparticles targeted to CD4+ T cells or podocytes (anti-podocin), we compared findings with vehicle-treated controls. TLS-associated inflammation and maturation were quantified by mean fluorescence intensity of CD3, CD20, Ki67, and \u03b1-SMA. Across genetic and targeted-treatment arms, CaMK4 inhibition reduced all assessed markers, with uniform suppression of CD20 signal, highlighting a key role for B cells in TLS maintenance. Notably, podocyte-targeted KN93 most strongly suppressed TLS-like formation, implicating podocyte-driven pathways in interstitial inflammation and lymphoid neogenesis through previously underappreciated mechanisms. These data identify CaMK4 as a regulator of TLS-like architecture in LN and support the translational potential of cell-targeted CaMK4 inhibition to disrupt local immune recruitment while limiting systemic toxicity.<\/jats:p>","DOI":"10.3390\/ijms27073190","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:34:08Z","timestamp":1774974848000},"page":"3190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cell-Targeted Inhibition of CaMK4 Suppresses Tertiary Lymphoid-like Structure Development in Lupus-Prone Mice"],"prefix":"10.3390","volume":"27","author":[{"given":"Simin","family":"Jamaly","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway"},{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad","family":"Rakaee","sequence":"additional","affiliation":[{"name":"Department of Cancer Genetics, Oslo University Hospital, Radiumhospitalet, 0310 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8794-7106","authenticated-orcid":false,"given":"Kunihiro","family":"Ichinose","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayaho","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Otomo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-1358","authenticated-orcid":false,"given":"Maria G.","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-2360","authenticated-orcid":false,"given":"George C.","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ard.2025.09.007","article-title":"EULAR recommendations for the management of systemic lupus erythematosus with kidney involvement: 2025 update","volume":"85","author":"Fanouriakis","year":"2026","journal-title":"Ann. 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