{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:19:41Z","timestamp":1790338781313,"version":"4.1.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dimethyl fumarate (DMF; trade name Tecfidera) is an oral formulation of the fumaric acid ester that is Food and Drug Administration approved for treatment of relapsing-remitting multiple sclerosis. To better understand the therapeutic effects of Tecfidera and its rare side effect of progressive multifocal leukoencephalopathy, we conducted cross-sectional and longitudinal studies by immunophenotyping cells from peripheral blood (particularly T lymphocytes) derived from untreated and 4\u20136 and 18\u201326 mo Tecfidera-treated stable relapsing-remitting multiple sclerosis patients using multiparametric flow cytometry. The absolute numbers of CD4 and CD8 T cells were significantly decreased and the CD4\/CD8 ratio was increased with DMF treatment. The proportions of both effector memory T cells and central memory T cells were reduced, whereas naive T cells increased in treated patients. T cell activation was reduced with DMF treatment, especially among effector memory T cells and effector memory RA T cells. Th subsets Th1 (CXCR3+), Th17 (CCR6+), and particularly those expressing both CXCR3 and CD161 were reduced most significantly, whereas the anti-inflammatory Th2 subset (CCR3+) was increased after DMF treatment. A corresponding increase in IL-4 and decrease in IFN-\u03b3 and IL-17\u2013expressing CD4+ T cells were observed in DMF-treated patients. DMF in vitro treatment also led to increased T cell apoptosis and decreased activation, proliferation, reactive oxygen species, and CCR7 expression. Our results suggest that DMF acts on specific memory and effector T cell subsets by limiting their survival, proliferation, activation, and cytokine production. Monitoring these subsets could help to evaluate the efficacy and safety of DMF treatment.<\/jats:p>","DOI":"10.4049\/jimmunol.1601532","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T20:50:20Z","timestamp":1488574220000},"page":"3069-3080","source":"Crossref","is-referenced-by-count":167,"title":["Dimethyl Fumarate Selectively Reduces Memory T Cells and Shifts the Balance between Th1\/Th17 and Th2 in Multiple Sclerosis Patients"],"prefix":"10.1093","volume":"198","author":[{"given":"Qi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-3035","authenticated-orcid":false,"given":"Guangmei","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A","family":"Dowling","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven K","family":"Lundy","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School , Ann Arbor, MI 48109"},{"name":"Graduate Program in Immunology, Program in Biomedical Sciences, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Mao-Draayer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan Medical School , Ann Arbor, MI 48109"},{"name":"Graduate Program in Immunology, Program in Biomedical Sciences, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,4,15]]},"reference":[{"key":"2025030615090213900_r1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s00415-008-1003-7","article-title":"Interplay between mechanisms of damage and repair in multiple sclerosis","volume":"255","author":"Stadelmann","year":"2008","journal-title":"J. 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