{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:16:54Z","timestamp":1768511814123,"version":"3.49.0"},"posted":{"date-parts":[[2024,6,24]]},"group-title":"Immunology","reference-count":37,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Psoriasis (PsO) and Psoriatic arthritis (PsA) are immune-mediated inflammatory diseases affecting the skin and joints. Approximately, 30% of patients with PsO develop PsA over time with both conditions being associated with elevated tumor necrosis factor-alpha (TNF-\u03b1) expression. TNF-\u03b1 mediates its effect through two membrane receptors, TNFR1 and TNFR2. While current TNF-\u03b1-neutralizing agents, targeting both TNFR1 and TNFR2 receptors, constitute the primary treatment for psoriatic diseases, their long-term use is limited due to an increase in opportunistic infections, tuberculosis reactivation and malignancies likely attributed to TNFR1 inactivation.<\/jats:p>\n                <jats:p>Recent findings suggest a pivotal role of TNFR2 in psoriatic disease, as evidenced by its amelioration in global TNFR2-knockout (TNFR2KO) mice, but not in TNFR1KO mice. The diminished disease phenotype in TNFR2KO mice is accompanied by a decrease in DC populations. However, the specific contribution of TNFR2 in dendritic cells (DCs) remains unclear. Here, utilizing a mannan-oligosaccharide (MOS)-induced PsA model, we demonstrate a significant reduction in PsA-like skin scaling and joint inflammation in dendritic cell-specific TNFR2 knockout mice (DC-TNFR2KO). Notably, MOS treatment in control mice (TNFR2 fl\/fl) led to an increase in conventional type 1 dendritic cells (cDC1) population in the spleen, a response inhibited in DC-TNFR2KO mice. Furthermore, DC-TNFR2KO mice exhibited reduced levels of interleukin-12 (IL-12), a Th1 cell activator, as well as diminished Th1 cells, and interferon-gamma (IFN-\u03b3) levels in the serum compared to controls following MOS stimulation.<\/jats:p>\n                <jats:p>In summary, our study provides compelling evidence supporting the role of TNFR2 in promoting PsA-like inflammation through cDC1\/Th1 activation pathways.<\/jats:p>","DOI":"10.1101\/2024.06.20.598545","type":"posted-content","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T17:55:15Z","timestamp":1719251715000},"source":"Crossref","is-referenced-by-count":1,"title":["Targeting dendritic cell-specific TNFR2 improves skin and joint inflammation by inhibiting IL-12\/ IFN-\u03b3 pathways in a mouse model of psoriatic arthritis"],"prefix":"10.64898","author":[{"given":"Raminderjit","family":"Kaur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Brambilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0761-2590","authenticated-orcid":false,"given":"Unnikrishnan M.","family":"Chandrasekharan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Elaine Husni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024062607250859000_2024.06.20.598545v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2015.07.001"},{"issue":"10136","key":"2024062607250859000_2024.06.20.598545v1.2","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1016\/S0140-6736(18)30830-4","article-title":"The pathogenesis of psoriatic 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Mannan induces ROS-regulated, IL-17A\u2013dependent psoriasis arthritis-like disease in mice. Proc Natl Acad Sci [Internet]. 2014 Sep 2 [cited 2024 Feb 23];111(35). 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