IL-21 promotes CD4 T cell responses by phosphatidylinositol 3-kinase-dependent upregulation of CD86 on B cells.
IL-21 promotes CD4 T cell responses by phosphatidylinositol 3-kinase-dependent upregulation of CD86 on B cells.
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DOI：
10.4049/jimmunol.1302082
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发表时间：
2014-03-01
期刊：
影响因子：
--
通讯作者：
Walker LS
中科院分区：
文献类型：
--
作者：
Attridge K;Kenefeck R;Wardzinski L;Qureshi OS;Wang CJ;Manzotti C;Okkenhaug K;Walker LS
细胞因子IL-21是一种有效的免疫调节剂，对多种细胞类型具有不同的作用机制。IL-21在临床上用于促进肿瘤排斥反应，并且是在自身免疫情况下中和的新兴靶标。尽管具有临床潜力，但IL-21的生物学作用尚未完全了解，这种多效性细胞因子的全方位作用仍有待发现。在这项研究中，我们确定了一个新的作用IL-21作为诱导剂的共刺激配体CD 86对B淋巴细胞。CD86通过T细胞表达的CD28提供关键信号，促进T细胞响应Ag接合而活化。CD86的表达水平在体内受到严格调节，通过调节性T细胞主动降低，并响应于病原体来源的信号而增加。在这项研究中，我们证明了IL-21可以通过STAT3和PI3K依赖性机制触发有效和持续的CD86上调。我们发现，升高的CD86表达具有功能性后果的大小的CD4 T细胞反应在体外和体内。这些数据指出，CD86上调是IL-21可引起免疫调节作用的另一种机制。
The cytokine IL-21 is a potent immune modulator with diverse mechanisms of action on multiple cell types. IL-21 is in clinical use to promote tumor rejection and is an emerging target for neutralization in the setting of autoimmunity. Despite its clinical potential, the biological actions of IL-21 are not yet fully understood and the full range of effects of this pleiotropic cytokine are still being uncovered. In this study, we identify a novel role for IL-21 as an inducer of the costimulatory ligand CD86 on B lymphocytes. CD86 provides critical signals through T cell–expressed CD28 that promote T cell activation in response to Ag engagement. Expression levels of CD86 are tightly regulated in vivo, being actively decreased by regulatory T cells and increased in response to pathogen-derived signals. In this study, we demonstrate that IL-21 can trigger potent and sustained CD86 upregulation through a STAT3 and PI3K-dependent mechanism. We show that elevated CD86 expression has functional consequences for the magnitude of CD4 T cell responses both in vitro and in vivo. These data pinpoint CD86 upregulation as an additional mechanism by which IL-21 can elicit immunomodulatory effects.
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影响因子：
30.5
作者：
Luethje, Katja;Kallies, Axel;Nutt, Stephen L.
通讯作者：
Nutt, Stephen L.
DOI：
10.4049/jimmunol.1102885
发表时间：
2012-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Good-Jacobson KL;Song E;Anderson S;Sharpe AH;Shlomchik MJ
通讯作者：
Shlomchik MJ
影响因子：
4.4
作者：
Clough, Louise E.;Wang, Chun Jing;Walker, Lucy S. K.
通讯作者：
Walker, Lucy S. K.
影响因子：
20.3
作者：
Gowda, Aruna;Roda, Julie;Byrd, John C.
通讯作者：
Byrd, John C.
影响因子：
20.3
作者：
Curiel, RE;Garcia, CS;Espinoza-Delgado, I
通讯作者：
Espinoza-Delgado, I