{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:27:27Z","timestamp":1760059647120,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MSD-AVENIR (\u201cBioric\u201d)"},{"name":"R\u00e9gion Occitanie: (\u201cPrematuration Program\u201d)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lymphotoxin-alpha (LT\u03b13) is a soluble cytokine of the TNF superfamily. Its role in inflammation and arthritis is not well known. Macrophages are important in K\/BxN Serum-Transfer Arthritis (STA) and rheumatoid arthritis (RA). Anti-TNF monoclonal antibodies as well as etanercept (ETA), a soluble TNF receptor II that also neutralizes LT\u03b13, are efficient in the treatment of RA. Objectives: To evaluate the role of LT\u03b13 in macrophage phenotypes and in arthritis. Methods: Macrophages were cultured in the presence of recombinant LT\u03b13, and their phenotypes were studied. The clinical effect of blocking LT\u03b13 in STA was evaluated, as well as the effect of switching from anti-TNF monoclonal antibodies to etanercept in the \u201cROC\u201d register of RA patients. Results: We showed that recombinant LT\u03b13 was capable of directing mouse and human macrophages towards a pro-inflammatory \u201cM1\u201d phenotype. In K\/BxN STA, ETA decreased clinical score and joint swelling. Anti-LT\u03b13 reduced arthritis only in TNF-KO mice, indicating that the effect of LT\u03b13 was visible in the absence of TNF. The \u201cROC\u201d register indicated that switching anti-TNF mAb to ETA did not induce clinical and biological improvement in RA. Conclusion: We show a pro-inflammatory role for LT\u03b13 in murine and human macrophages. The neutralization of both TNF and LT\u03b13 is not beneficial in the treatment of RA.<\/jats:p>","DOI":"10.3390\/ijms26136355","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T07:42:06Z","timestamp":1751355726000},"page":"6355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evidence for Pro-Inflammatory Activity of LT\u03b13 on Macrophages: Significance for Experimental Arthritis and for Therapeutic Switching in Rheumatoid Arthritis Patients"],"prefix":"10.3390","volume":"26","author":[{"given":"Ariane","family":"Benezech","sequence":"first","affiliation":[{"name":"INSERM U1043, Centre de Physiopathologie de Toulouse Purpan, 31059 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques-Eric","family":"Gottenberg","sequence":"additional","affiliation":[{"name":"Service de Rhumatologie, CHU de Strasbourg, 67098 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yannick","family":"Degbo\u00e9","sequence":"additional","affiliation":[{"name":"INSERM U1043, Centre de Physiopathologie de Toulouse Purpan, 31059 Toulouse, France"},{"name":"Centre de Rhumatologie, CHU de Toulouse, 31059 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-2087","authenticated-orcid":false,"given":"Andrey","family":"Kruglov","sequence":"additional","affiliation":[{"name":"Deutsches Rheuma-Forschungszentrum, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Grogan","sequence":"additional","affiliation":[{"name":"Genentech, San Francisco, CA 94080, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2524-1762","authenticated-orcid":false,"given":"Fabienne","family":"Briand-M\u00e9sange","sequence":"additional","affiliation":[{"name":"INSERM U1043, Centre de Physiopathologie de Toulouse Purpan, 31059 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8890-9099","authenticated-orcid":false,"given":"Alain","family":"Cantagrel","sequence":"additional","affiliation":[{"name":"INSERM U1043, Centre de Physiopathologie de Toulouse Purpan, 31059 Toulouse, France"},{"name":"Centre de Rhumatologie, CHU de Toulouse, 31059 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adeline","family":"Ruyssen-Witrand","sequence":"additional","affiliation":[{"name":"Centre de Rhumatologie, CHU de Toulouse, 31059 Toulouse, France"},{"name":"Inserm UMR 1027, CHU Purpan, 31062 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Luc","family":"Davignon","sequence":"additional","affiliation":[{"name":"INSERM U1043, Centre de Physiopathologie de Toulouse Purpan, 31059 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nri2094","article-title":"Cytokines in the pathogenesis of rheumatoid arthritis","volume":"7","author":"McInnes","year":"2007","journal-title":"Nat. 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