{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:52:14Z","timestamp":1787165534244,"version":"build-2736575974"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with T cell dysregulation. The lymphocyte-activation gene (LAG)-3 is one of the regulatory receptors expressed on T cells in a soluble form. LAG-3 expression on T cells was analyzed in vitro in PsA patients with minimal disease activity (MDA), active disease (non-MDA) and healthy controls. In cultured in-vitro peripheral blood mononuclear cells (PBMCs), LAG-3 expression on CD4+ T cells was similar in both MDA PsA patients (7.5\u00a0\u00b1\u00a00.9) (n\u00a0=\u00a014) and healthy controls (7.8\u00a0\u00b1\u00a00.6) (n\u00a0=\u00a015), but significantly lower in non-MDA PsA patients (3.1\u00a0\u00b1\u00a00.3) (n\u00a0=\u00a013) (p\u00a0&amp;lt;\u00a00.0001). An inverse correlation between PsA clinical disease activity and %CD4+LAG-3+ T cells in vitro was observed (composite psoriatic disease activity index r\u00a0=\u00a0\u22120.47, p\u00a0&amp;lt;\u00a00.02 and psoriatic arthritis disease activity score, r\u00a0=\u00a0\u22120.51, p\u00a0&amp;lt;\u00a00.008). In-vitro co-culture of CD4+ T cells with anti-tumor necrosis factor (TNF) or anti-interleukin (IL)-17A had no effect on LAG-3+ expression in MDA PsA patients and healthy controls. In non-MDA patients, anti-TNF, but not anti-IL-17A, restored the %CD4+LAG-3+ T cells (7.9\u00a0\u00b1\u00a00.9 and 3.2\u00a0\u00b1\u00a00.4, respectively) (p\u00a0&amp;lt;\u00a00.0004). Lower soluble LAG-3 levels were found in sera of naive to biological PsA patients (n\u00a0=\u00a039) compared to healthy controls (n\u00a0=\u00a035) (p\u00a0&amp;lt;\u00a00.03). Impaired LAG-3 on CD4+ T cells may reflect active PsA disease state. Anti-TNFs have potency to up-regulate the CD4+LAG-3+ T cells in vitro.<\/jats:p>","DOI":"10.1111\/cei.13646","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T09:46:48Z","timestamp":1627292808000},"page":"173-183","source":"Crossref","is-referenced-by-count":20,"title":["CD4+LAG-3+ T cells are decreased in active psoriatic arthritis patients and their restoration\n                    <i>in vitro<\/i>\n                    is mediated by TNF inhibitors"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-7184","authenticated-orcid":false,"given":"Smadar","family":"Gertel","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Polachek","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Furer","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Levartovsky","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ori","family":"Elkayam","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"2021121100032182200_cei13646-bib-0001","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1136\/ard.2008.102053","article-title":"Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment","volume":"69","author":"Coates","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"2021121100032182200_cei13646-bib-0002","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.autrev.2014.11.012","article-title":"T cell responses in psoriasis and psoriatic arthritis","volume":"14","author":"Diani","year":"2015","journal-title":"Autoimmun Rev"},{"key":"2021121100032182200_cei13646-bib-0003","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nri2138","article-title":"Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans","volume":"7","author":"Roncarolo","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"2021121100032182200_cei13646-bib-0004","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"2021121100032182200_cei13646-bib-0005","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s13075-017-1364-3","article-title":"Abatacept reduces synovial regulatory T-cell expression in patients with psoriatic arthritis","volume":"19","author":"Szentpetery","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"2021121100032182200_cei13646-bib-0006","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nm.2425","article-title":"Foxp3+ follicular regulatory T cells control the germinal center response","volume":"17","author":"Linterman","year":"2011","journal-title":"Nat Med"},{"key":"2021121100032182200_cei13646-bib-0007","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). 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