Interferon-β suppresses murine Th1 cell function in the absence of antigen-presenting cells.
Interferon-β suppresses murine Th1 cell function in the absence of antigen-presenting cells.
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DOI：
10.1371/journal.pone.0124802
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Rangachari M
中科院分区：
文献类型：
--
作者：
Boivin N;Baillargeon J;Doss PM;Roy AP;Rangachari M
干扰素-β是治疗复发-缓解型多发性硬化症的一线疗法。然而，其免疫抑制的作用机制仍不完全清楚。虽然干扰素-β通过促进抗原提呈细胞释放IL-27等免疫调节细胞因子来抑制炎性髓鞘抗原反应性T细胞的功能，但其对炎性CD_4+Th1细胞的直接作用尚不清楚。在这里，我们确定干扰素-β在缺乏APC的情况下抑制小鼠干扰素-γ+Th1细胞功能。CD4+T细胞表达I型干扰素受体，干扰素-β在无刺激条件下可抑制Th1细胞的增殖。干扰素-β治疗的髓鞘抗原特异性Th1细胞在转移到淋巴细胞缺陷的RAG1-/-小鼠后，诱导严重的实验性自身免疫性脑脊髓炎(EAE)的能力受损。当极化的Th1细胞在缺乏APC的情况下用干扰素-γ处理时，下调干扰素-β和IL-2，上调负调控受体TIM-3。此外，干扰素-β治疗Th1细胞上调STAT1的磷酸化，下调STAT4的磷酸化。我们的数据表明，产生干扰素-γ的Th1细胞直接对干扰素-β产生反应，并指出了一种新的干扰素-β介导的T细胞抑制机制，该机制不依赖于APC来源的信号。
Interferon (IFN)-β is a front-line therapy for the treatment of the relapsing-remitting form of multiple sclerosis. However, its immunosuppressive mechanism of function remains incompletely understood. While it has been proposed that IFN-β suppresses the function of inflammatory myelin antigen-reactive T cells by promoting the release of immunomodulatory cytokines such as IL-27 from antigen-presenting cells (APCs), its direct effects on inflammatory CD4+ Th1 cells are less clear. Here, we establish that IFN-β inhibits mouse IFN-γ+ Th1 cell function in the absence of APCs. CD4+ T cells express the type I interferon receptor, and IFN-β can suppress Th1 cell proliferation under APC-free stimulation conditions. IFN-β-treated myelin antigen-specific Th1 cells are impaired in their ability to induce severe experimental autoimmune encephalomyelitis (EAE) upon transfer to lymphocyte-deficient Rag1-/- mice. Polarized Th1 cells downregulate IFN-γ and IL-2, and upregulate the negative regulatory receptor Tim-3, when treated with IFN-β in the absence of APCs. Further, IFN-β treatment of Th1 cells upregulates phosphorylation of Stat1, and downregulates phosphorylation of Stat4. Our data indicate that IFN-γ-producing Th1 cells are directly responsive to IFN-β and point to a novel mechanism of IFN-β-mediated T cell suppression that is independent of APC-derived signals.
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影响因子：
5.4
作者：
Anderson, Ana C.;Lord, Graham M.;Dardalhon, Valerie;Lee, David H.;Sabatos-Peyton, Catherine A.;Glimcher, Laurie H.;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
--
作者：
JACOBS, L;JOHNSON, KP
通讯作者：
JOHNSON, KP
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
T-BET的丧失，但不是STAT1阻止了实验性自身免疫性脑脊髓炎的发展。
影响因子：
15.3
作者：
Bettelli, E;Sullivan, B;Szabo, SJ;Sobel, RA;Glimcher, H;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
56.9
作者：
Hwang, ES;Szabo, SJ;Glimcher, LH
通讯作者：
Glimcher, LH