Relapsing-Remitting Multiple Sclerosis Is Characterized by a T Follicular Cell Pro-Inflammatory Shift, Reverted by Dimethyl Fumarate Treatment

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dc.contributor.author Cunill, V.
dc.contributor.author Massot, M.
dc.contributor.author Clemente, A.
dc.contributor.author Calles, C.
dc.contributor.author Andreu, V.
dc.contributor.author Núñez, V.
dc.contributor.author López-Gómez, A.
dc.contributor.author Díaz, R.M.
dc.contributor.author Jiménez, M.L.R.
dc.contributor.author Pons, J.
dc.contributor.author Vives-Bauzà, C.
dc.contributor.author Ferrer, J.M.
dc.date.accessioned 2020-05-07T06:40:36Z
dc.date.available 2020-05-07T06:40:36Z
dc.identifier.uri http://hdl.handle.net/11201/152269
dc.description.abstract [eng] Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease, although several evidences also demonstrate a B cell involvement in its etiology. Follicular T helper (Tfh) cells, a CXCR5-expressing CD4+ T cell subpopulation, are essential in the regulation of B cell differentiation and maintenance of humoral immunity. Alterations in circulating (c)Tfh distribution and/or function have been associated with autoimmune diseases including MS. Dimethyl fumarate (DMF) is a recently approved first-line treatment for relapsing-remitting MS (RRMS) patients whose mechanism of action is not completely understood. The aim of our study was to compare cTfh subpopulations between RRMS patients and healthy subjects and evaluate the impact of DMF treatment on these subpopulations, relating them to changes in B cells and humoral response. We analyzed, by flow cytometry, the distribution of cTfh1 (CXCR3+CCR6-), cTfh2 (CXCR3-CCR6-), cTfh17 (CXCR3-CCR6+), and the recently described cTfh17.1 (CXCR3+CCR6+) subpopulations of CD4+ Tfh (CD45RA-CXCR5+) cells in a cohort of 29 untreated RRMS compared to healthy subjects. CD4+ non-follicular T helper (Th) cells (CD45RA-CXCR5-) were also studied. We also evaluated the effect of DMF treatment on these subpopulations after 6 and 12 months treatment. Untreated RRMS patients presented higher percentages of cTfh17.1 cells and lower percentages of cTfh2 cells consistent with a pro-inflammatory bias compared to healthy subjects. DMF treatment induced a progressive increase in cTfh2 cells, accompanied by a decrease in cTfh1 and the pathogenic cTfh17.1 cells. A similar decrease of non-follicular Th1 and Th17.1 cells in addition to an increase in the anti-inflammatory Th2 subpopulation were also detected upon DMF treatment, accompanied by an increase in naïve B cells and a decrease in switched memory B cells and serum levels of IgA, IgG2, and IgG3. Interestingly, this effect was not observed in three patients in whom DMF had to be discontinued due to an absence of clinical response. Our results demonstrate a possibly pathogenic cTfh pro-inflammatory profile in RRMS patients, defined by high cTfh17.1 and low cTfh2 subpopulations that is reverted by DMF treatment. Monitoring cTfh subsets during treatment may become a biological marker of DMF effectiveness.
dc.format application/pdf
dc.relation.isformatof https://doi.org/10.3389/fimmu.2018.01097
dc.relation.ispartof Frontiers In Immunology, 2018, vol. 9, p. 1-13
dc.rights , 2018
dc.subject.classification 57 - Biologia
dc.subject.other 57 - Biological sciences in general
dc.title Relapsing-Remitting Multiple Sclerosis Is Characterized by a T Follicular Cell Pro-Inflammatory Shift, Reverted by Dimethyl Fumarate Treatment
dc.type info:eu-repo/semantics/article
dc.date.updated 2020-05-07T06:40:36Z
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.identifier.doi https://doi.org/10.3389/fimmu.2018.01097


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