Analysis of gene profile, steady state proliferation and apoptosis of double-negative T cells in the periphery and gut epithelium provides new insights into the biological functions of the Fas pathway.
Analysis of gene profile, steady state proliferation and apoptosis of double-negative T cells in the periphery and gut epithelium provides new insights into the biological functions of the Fas pathway.
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DOI：
10.1007/s12026-009-8144-3
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发表时间：
2010-07
影响因子：
4.4
通讯作者：
Hamad AR
中科院分区：
文献类型：
--
作者：
Hamad AR
在分子和细胞水平上对Fas途径的了解已经取得了相当大的进展，但关于Fas途径的整体生物学作用的根本问题仍然没有解决。一个主要的问题是，为什么由Fas的lpr突变和FasL配体的gld突变引起的淋巴增殖主要是CD_4和CD_8双重阴性的αT细胞(DN T细胞)，否则它们是外周T细胞谱系中稀有的成分。第二个悬而未决的问题是，为什么Fas途径的失活会阻止器官特异性自身免疫(包括1型糖尿病和多发性硬化症)，同时导致全身淋巴增殖？了解这些过程的机制，可以揭示Fas途径生物学作用的重要方面，并可能具有重大的治疗意义。例如，揭示Fas途径失活如何阻止器官特异性自身免疫的基础可能会导致新的免疫治疗策略，在不导致免疫抑制的情况下促进自身耐受，因为Fas途径对T细胞激活不是必不可少的。在这里，我们将讨论我的实验室最近和新的发现，这些发现解决了这些问题，包括糖尿病肾病T细胞的性质，以及Fas通路在肠道上皮细胞隔离中的作用和潜在作用。
Considerable progress has been made in understanding the Fas pathway at the molecular and cellular levels, but fundamental questions about the overall biological role of the Fas pathway remain unresolved. A major question is why lymphoproliferation caused by the lpr mutation of Fas and gld mutation of FasL ligand (FasL) is dominated by CD4— and CD8— double negative α T cells (DN T cells) that are otherwise rare components of the peripheral T cell repertoire. A second unresolved question is why inactivation of the Fas pathway prevents organ specific autoimmunity (including as type 1 diabetes and multiple sclerosis) while causing systemic lymphoproliferation? Understanding the mechanisms of these processes, could uncover important aspects of the biological role of the Fas pathway and could have significant therapeutic implications. For example, revealing the basis of how inactivation of the Fas pathway prevents organ specific autoimmunity could lead to new immunotherapeutic strategies to promote self tolerance without causing immunosuppression, as the Fas pathway is not essential for T cell activation. Here we will discuss recent and new findings from my laboratory that address these questions including the nature of DN T cells and role and potential role of the Fas pathway in sequestration of DN T cells within the gut epithelium.
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影响因子：
6
作者：
Mohamood, Abdiaziz S.;Guler, Mehmet L.;Hamad, Abdel Rahim A.
通讯作者：
Hamad, Abdel Rahim A.
影响因子：
56.9
作者：
Bouillet, P;Metcalf, D;Strasser, A
通讯作者：
Strasser, A
影响因子：
64.8
作者：
DHEIN, J;WALCZAK, H;KRAMMER, PH
通讯作者：
KRAMMER, PH
影响因子：
64.5
作者：
Chervonsky, AV;Wang, Y;Matis, LA
通讯作者：
Matis, LA
DOI：
10.1016/j.bbrc.2005.04.025
发表时间：
2005-06-17
影响因子：
3.1
作者：
Inagaki-Ohara, K;Sawaguchi, A;Nawa, Y
通讯作者：
Nawa, Y