Dimethyl fumarate promotes B cell-mediated anti-inflammatory cytokine profile in B and T cells, and inhibits immune cell migration in patients with MS,Journal of Neuroimmunology

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Dimethyl fumarate promotes B cell-mediated anti-inflammatory cytokine profile in B and T cells, and inhibits immune cell migration in patients with MS
Journal of Neuroimmunology ( IF 2.9 ) Pub Date : 2020-06-01 , DOI: 10.1016/j.jneuroim.2020.577230
Eiman Najjar ₁ , Elsebeth Staun-Ram ₂ , Anat Volkowich ₃ , Ariel Miller ₂

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Dimethyl Fumarate (DMF), known for its mechanism of action targeting Nrf2 and related redox homeostasis, is an approved immunotherapy for patients with Multiple Sclerosis (PwMS) in the relapsing form. We assessed how DMF modulates immune cell functions, namely the cytokine profile of co-cultured B and T cells, and the chemokine-mediated migration of immune cells. Following DMF therapy, LTα+, TNFα+ and IFNγ+ B cells were reduced while TGFβ and IL10 expression elevated. B cells from DMF-treated patients increased TGFβ and LTα expression on T cells, while DMF directly reduced TNFα+ and IFNγ+ T cells. CXCL12/CXCL13-mediated migration of B cells, Monocytes, CD4 and CD8 T cells was reduced, with altered CXCR5 and CXCR4 expression. Induction of regulatory B and T cells and reduced migration of immune cells may be part of the beneficial mechanism of DMF in PwMS.

中文翻译：

富马酸二甲酯促进 B 细胞和 T 细胞中 B 细胞介导的抗炎细胞因子谱，并抑制 MS 患者的免疫细胞迁移

富马酸二甲酯 (DMF) 以其靶向 Nrf2 和相关氧化还原稳态的作用机制而闻名，是一种已批准的免疫疗法，用于复发型多发性硬化症 (PwMS) 患者。我们评估了 DMF 如何调节免疫细胞功能，即共培养的 B 和 T 细胞的细胞因子谱，以及趋化因子介导的免疫细胞迁移。DMF 治疗后，LTα+、TNFα+ 和 IFNγ+ B 细胞减少，而 TGFβ 和 IL10 表达升高。来自 DMF 治疗患者的 B 细胞增加了 T 细胞上的 TGFβ 和 LTα 表达，而 DMF 直接减少了 TNFα+ 和 IFNγ+ T 细胞。CXCL12/CXCL13 介导的 B 细胞、单核细胞、CD4 和 CD8 T 细胞迁移减少，CXCR5 和 CXCR4 表达改变。

更新日期：2020-06-01

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