Tim-1 stimulation of dendritic cells regulates the balance between effector and regulatory T cells.
Tim-1 stimulation of dendritic cells regulates the balance between effector and regulatory T cells.
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DOI：
10.1002/eji.201040993
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发表时间：
2011-06
影响因子：
5.4
通讯作者：
Kuchroo, Vijay K.
中科院分区：
文献类型：
--
作者：
Xiao, Sheng;Zhu, Bing;Jin, Hulin;Zhu, Chen;Umetsu, Dale T.;DeKruyff, Rosemarie H.;Kuchroo, Vijay K.
我们表明，蒂姆-1，最初报告的表达CD 4 + T细胞，组成性表达的树突状细胞（DC），其表达进一步增加后，DC成熟。Tim-1信号传导到DC上调共刺激分子表达和促炎细胞因子产生，从而促进效应T细胞应答，同时抑制Foxp 3 + Treg应答。相比之下，T细胞中的Tim-1信号传导仅调节Th 2应答。使用高亲合力/激动性抗Tim-1抗体作为共佐剂增强了DC的免疫原性功能，降低了Treg细胞的抑制功能，并显著增加了体内促炎性Th 17应答。用高而非低亲合力抗Tim-1治疗不仅可预防易感小鼠的实验性自身免疫性脑脊髓炎（EAE），而且可破坏耐受性并诱导遗传抗性小鼠品系的EAE。这些发现表明Tim-1在调节DC功能中具有重要作用，从而将效应T细胞和调节T细胞之间的平衡转向增强的免疫应答。通过了解Tim-1调节DC和T细胞反应的机制，我们可以阐明Tim-1作为自身免疫，癌症和感染性疾病治疗靶点的潜在用途。
We show that Tim-1, initially reported to be expressed on CD4+ T cells, is constitutively expressed on dendritic cells (DC) and that its expression further increases after DC maturation. Tim-1 signaling into DC upregulates costimulatory molecule expression and proinflammatory cytokine production, thereby promoting effector T cell responses, while inhibiting Foxp3+ Treg responses. By contrast, Tim-1 signaling in T cells only regulates Th2 responses. Using a high-avidity/agonistic anti-Tim-1 antibody as a co-adjuvant enhances the immunogenic function of DC, decreases the suppressive function of Treg cells, and substantially increases proinflammatory Th17 responses in vivo. The treatment with high-but not low-, avidity anti-Tim-1 not only worsens experimental autoimmune encephalomyelitis (EAE) in susceptible mice but also breaks tolerance and induces EAE in a genetically resistant strain of mice. These findings indicate that Tim-1 has an important role in regulating DC function, and thus shifts the balance between effector and regulatory T cells towards an enhanced immune response. By understanding the mechanisms by which Tim-1 regulates DC and T cell responses, we may clarify the potential utility of Tim-1 as a target of therapy against autoimmunity, cancer and infectious diseases.
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DOI：
10.1073/pnas.0404444101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Reddy, J;Illes, Z;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
82.9
作者：
Korn, Thomas;Reddy, Jayagopala;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
11.4
作者：
Kaplan, G;Totsuka, A;Feinstone, SM
通讯作者：
Feinstone, SM
影响因子：
4.4
作者：
Nakamura, K;Kitani, A;Strober, W
通讯作者：
Strober, W
影响因子：
4.8
作者：
Ichimura, T;Bonventre, JV;Sanicola, M
通讯作者：
Sanicola, M