Glucose-Regulated Protein 78-Induced Myeloid Antigen-Presenting Cells Maintained Tolerogenic Signature upon LPS Stimulation.
Glucose-Regulated Protein 78-Induced Myeloid Antigen-Presenting Cells Maintained Tolerogenic Signature upon LPS Stimulation.
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葡萄糖调节蛋白 78 诱导的骨髓抗原呈递细胞在 LPS 刺激下维持耐受性特征
DOI：
10.3389/fimmu.2016.00552
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发表时间：
2016
影响因子：
7.3
通讯作者：
Shen G
中科院分区：
文献类型：
--
作者：
Yang M;Zhang F;Qin K;Wu M;Li H;Zhu H;Ning Q;Lei P;Shen G
78 kDa葡萄糖调节蛋白(GRP78)是应激诱导的伴侣蛋白，主要存在于内质网中。GRP78被描述为在细胞应激时释放，并具有抗炎或有利于消退炎症的细胞外特性。由于抗原提呈细胞在启动获得性免疫反应和诱导自身耐受中起着关键作用，因此，我们研究了GRP78对小鼠髓系APC(CD11c+细胞)成熟的影响。结果表明，CD11c+细胞可与AF488标记的GRP78结合，GRP78处理可诱导出与未成熟细胞相当的耐受表型。此外，当暴露于脂多糖时，GRP78处理的CD11c+细胞(DCGrp78)不具有成熟的树突状细胞表型。DCGrp78诱导的T细胞在体外和体外表现出增殖抑制，伴随着胰腺十二指肠淋巴结中CD4+CD25+FoxP3+细胞的扩张，并诱导T细胞凋亡。上述工作表明，GRP78是一种免疫调节分子，可能有助于炎症的消退。因此，它可能有助于诱导持久的耐受，对移植的同种异体移植物和自身免疫性疾病(如I型糖尿病)具有潜在的治疗益处。
The 78-kDa glucose-regulated protein (Grp78) is stress-inducible chaperone that mostly reside in the endoplasmic reticulum. Grp78 has been described to be released at times of cellular stress and as having extracellular properties that are anti-inflammatory or favor the resolution of inflammation. As antigen-presenting cells (APCs) play a critical role in both the priming of adaptive immune responses and the induction of self-tolerance, herein, we investigated the effect of Grp78 on the maturation of murine myeloid APCs (CD11c+ cells). Results showed that CD11c+ cells could be bound by AF488-labeled Grp78 and that Grp78 treatment induced a tolerogenic phenotype comparable to immature cells. Furthermore, when exposed to lipopolysaccharide, Grp78-treated CD11c+ cells (DCGrp78) did not adopt a mature dendritic cell phenotype. DCGrp78-primed T cells exhibited reduced proliferation along with a concomitant expansion of CD4+CD25+FoxP3+ cells in pancreaticoduodenal lymph nodes and induction of T cell apoptosis in vitro and ex vivo. The above work suggests that Grp78 is an immunomodulatory molecule that could aid resolution of inflammation. It may thus contribute to induce durable tolerance to be of potential therapeutic benefit in transplanted allogeneic grafts and autoimmune diseases such as type I diabetes.
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影响因子：
4.4
作者：
Li, Qingsheng;Harden, Jamie L.;Egilmez, Nejat K.
通讯作者：
Egilmez, Nejat K.
影响因子：
--
作者：
Maldonado, Roberto A.;von Andrian, Ulrich H.
通讯作者：
von Andrian, Ulrich H.
影响因子：
7.5
作者：
Pfaffenbach KT;Lee AS
通讯作者：
Lee AS
影响因子：
6.2
作者：
Lu, L;McCaslin, D;Thomson, AW
通讯作者：
Thomson, AW
影响因子：
56.9
作者：
Pasare, C;Medzhitov, R
通讯作者：
Medzhitov, R