Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells.
Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells.
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DOI：
10.1016/j.immuni.2008.09.018
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发表时间：
2008-11-14
期刊：
影响因子：
32.4
通讯作者：
Benoist C
中科院分区：
文献类型：
--
作者：
Hill JA;Hall JA;Sun CM;Cai Q;Ghyselinck N;Chambon P;Belkaid Y;Mathis D;Benoist C
调节性T（Treg）细胞的CD 4 + Foxp 3+谱系在控制免疫和自身免疫应答中起关键作用。Treg细胞主要起源于胸腺中的T细胞分化期间，但成熟T淋巴细胞向Foxp 3阳性的转化可通过几种方式引起，包括在体外存在转化生长因子（TGF）β的情况下活化。视黄酸（RA）是一种普遍存在的形态原，对肠道免疫系统发挥特定的牧羊作用，可增加TGFβ诱导的Foxp 3表达，本研究显示该作用通过RA受体（RAR）α介导。RA的部分影响可能是由于其下调IL-6受体的能力，IL-6是一种抑制Foxp 3表达的细胞因子，但这种影响似乎相对次要。相反，RA对具有CD 44 hi表型的CD 4+细胞群体产生负面影响，类似于记忆或效应细胞，其抑制TGFβ诱导的幼稚CD 4 + T细胞的转化。这种“逆转换”活性至少部分地通过一组细胞因子（IL-4、IL-21、IFNγ）的合成介导，所述细胞因子组合对Foxp 3诱导具有有效的抑制作用。RA通过RARα诱导CD 44 hi细胞中细胞因子表达的整个程序的协调关闭。通过转移RA敏感性OT-II T细胞确定了该观察结果的体内相关性，该T细胞在RARα缺陷型宿主中显示出较低的转化为Foxp 3+的有效性。因此，CD 44 hi T细胞可以主动抑制Foxp 3的诱导，并且这种平衡可以被RA改变或微调。
The CD4+Foxp3+ lineage of regulatory T (Treg) cells plays a key role in controlling immune and autoimmune responses. Treg cells originate primarily during T cell differentiation in the thymus, but conversion of mature T lymphocytes to Foxp3-positivity can be elicited by several means, including activation in the presence of transforming growth factor (TGF)β in vitro. Retinoic Acid (RA), the ubiquitous morphogen that exerts a particular shepherding effect on the gut immune system, increases TGFβ–induced expression of Foxp3, an effect shown here to be mediated through RA receptor (RAR)α. Part of RA’s influence may be due to it’s ability to down-modulate the receptor for IL-6, a cytokine that inhibits Foxp3 expression, but this effect appeared to be of relatively minor importance. Rather, RA negatively affected a population of CD4+ cells with a CD44hi phenotype, akin to that of memory or effector cells, which inhibited the TGFβ-induced conversion of naïve CD4+ T cells. This “contra-conversion” activity was mediated, at least in part, through the synthesis of a set of cytokines (IL-4, IL-21, IFNγ), which in combination had a potent dampening effect on Foxp3 induction. RA, via RARα, elicited a coordinated shut-down of the whole program of cytokine expression in CD44hi cells. The in vivo relevance of this observation was established by transferring RA-sensitive OT-II T cells, which showed less effective conversion to Foxp3+ in RARα-deficient hosts. Thus, CD44hi T cells can actively restrain the induction of Foxp3, and this balance can be shifted or fine tuned by RA.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
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作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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