Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naïve T cells into cytokine-producing mature T cells.
Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naïve T cells into cytokine-producing mature T cells.
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DOI：
10.1371/journal.pone.0031465
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mizutani H
中科院分区：
文献类型：
--
作者：
Tsuda K;Yamanaka K;Kitagawa H;Akeda T;Naka M;Niwa K;Nakanishi T;Kakeda M;Gabazza EC;Mizutani H
根据干扰素-γ和IL-4等细胞因子的产生，T细胞被分为Th1或Th2亚群。Th17谱系和调节性T细胞的发现将Th1/Th2平衡的简单概念转变为局部和系统免疫活动的四向机制途径。临床上，免疫抑制剂阻断细胞因子信号或非特异性抑制细胞因子优势是炎症性T细胞介导疾病的一线治疗方法。环孢素A(CsA)和他克莫司(Tac)是治疗自身免疫性疾病、银屑病和特应性疾病的常用免疫抑制剂。许多研究表明，这些化合物抑制钙依赖的磷酸酶钙调神经磷酸酶的激活，从而抑制T细胞的激活。虽然CsA和Tac是常用的药物，但其药理机制尚未完全阐明。在本研究中，我们重点研究了CsA和Tac对纯化的人类记忆CD4+T细胞分泌细胞因子的影响，以及幼稚T细胞向产生细胞因子的记忆T细胞的分化。CsA或Tac显著抑制记忆T细胞产生干扰素-γ、IL-4和IL-17。这些化合物还抑制T细胞分化为Th1、Th2和Th17亚群，即使在低浓度使用时也是如此。这项研究提供了有关CsA和Tac作为免疫抑制剂的临床疗效的关键信息。
T cells have been classified as belonging to the Th1 or Th2 subsets according to the production of defining cytokines such as IFN-γ and IL-4. The discovery of the Th17 lineage and regulatory T cells shifted the simple concept of the Th1/Th2 balance into a 4-way mechanistic pathway of local and systemic immunological activity. Clinically, the blockage of cytokine signals or non-specific suppression of cytokine predominance by immunosuppressants is the first-line treatment for inflammatory T cell-mediated disorders. Cyclosporine A (CsA) and Tacrolimus (Tac) are commonly used immunosuppressants for the treatment of autoimmune disease, psoriasis, and atopic disorders. Many studies have shown that these compounds suppress the activation of the calcium-dependent phosphatase calcineurin, thereby inhibiting T-cell activation. Although CsA and Tac are frequently utilized, their pharmacological mechanisms have not yet been fully elucidated. In the present study, we focused on the effects of CsA and Tac on cytokine secretion from purified human memory CD4+T cells and the differentiation of naïve T cells into cytokine-producing memory T cells. CsA or Tac significantly inhibited IFN-γ, IL-4, and IL-17 production from memory T cells. These compounds also inhibited T cell differentiation into the Th1, Th2, and Th17 subsets, even when used at a low concentration. This study provided critical information regarding the clinical efficacies of CsA and Tac as immunosuppressants.
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DOI：
10.1084/jem.179.1.299
发表时间：
1994-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Seder RA;Germain RN;Linsley PS;Paul WE
通讯作者：
Paul WE
影响因子：
1.2
作者：
Kobayashi, Tetsuro;Momoi, Yasuyuki;Iwasaki, Toshiroh
通讯作者：
Iwasaki, Toshiroh
影响因子：
5.2
作者：
Schulze-Koops, H;Kalden, JK
通讯作者：
Kalden, JK
影响因子：
6.5
作者：
Austin, LM;Ozawa, M;Krueger, JG
通讯作者：
Krueger, JG
DOI：
10.1159/000323299
发表时间：
2011-01-01
期刊：
PATHOGENESIS AND MANAGEMENT OF ATOPIC DERMATITIS
影响因子：
--
作者：
Yamanaka, Kei-ichi;Mizutani, Hitoshi
通讯作者：
Mizutani, Hitoshi