Heat shock protein gp96 and Treg responses

摘要 热休克蛋白（HSP）gp96具有免疫原性。根据抗原呈递细胞（APC） 在细胞外环境中由gp96靶向，这些免疫应答可以是与Th1或Th2相反的。 Treg类型。这些免疫应答已被用于癌症和感染性疾病的免疫治疗。 疾病或自身免疫性疾病。我们已经表明，gp96受体，CD91，是由 常规树突状细胞（cDC），其允许由gp96陪伴的抗原的交叉呈递， 用于提供Th1应答的共刺激。我们最近发现了CD91在 浆细胞样树突状细胞（pDC）。目前还没有关于pDC如何影响gp96介导的细胞凋亡的信息。 免疫反应，特别是调节性T细胞反应。我们的假设是 pDC通过gp96经由CD91导致细胞内信号传导和与引发相关的分子的上调 和稳定Treg功能。我们的研究探索了gp96如何与各种APC群体结合， 原位，pDC的细胞内信号传导，以及引发背景下gp96激活的pDC的表型 增强其功能。这种途径不仅对肿瘤的发展有影响， 感染，但在自身免疫和这些疾病的免疫治疗。

Abstract The heat shock protein (HSP) gp96 is immunogenic. Depending on which antigen presenting cell (APC) is targeted by gp96 in the extracellular environment, these immune responses can be opposingly of the Th1 or Treg type. These immune responses have been harnessed for the immunotherapy of cancer and infectious disease or autoimmune disease respectively. We have shown that the gp96 receptor, CD91, is expressed by conventional dendritic cell (cDCs) which allows for cross-presentation of the antigens chaperoned by gp96 and for provision of co-stimulation for Th1 responses. We have recently uncovered CD91 expression on plasmacytoid dendritic cells (pDCs). There is currently no information on how pDCs influence gp96-mediated immune responses and specifically, how Treg responses are modulated. Our hypothesis is that engagement of pDCs by gp96 via CD91 leads to intracellular signaling and upregulation of molecules associated with priming and stabilization of Treg function. Our studies here explore how gp96 engages the various APC populations in situ, the intracellular signaling with pDCs, and the phenotype of gp96-activated pDCs in the context of priming Tregs and enhancement of their function. This pathway has consequences not only for tumor development and infection but in autoimmunity, and in immunotherapy of these diseases.