Immunomodulatory cross-talk between conjunctival goblet cells and dendritic cells.

Immunomodulatory cross-talk between conjunctival goblet cells and dendritic cells.
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DOI:
10.1371/journal.pone.0120284
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Masli S
Masli S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Contreras-Ruiz L;Masli S

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杯状细胞是粘膜组织的分泌性上皮细胞,其通过表达和分泌可溶性粘蛋白来提供对环境因子或病原体的保护。这些细胞的损失与几种慢性粘膜炎性疾病有关。虽然已证实杯状细胞可将抗原从腔表面转移到肠粘膜中的基质细胞,但尚不清楚杯状细胞是否有助于调节免疫应答。在这项研究中,我们报告,类似于肠和呼吸道粘膜上皮细胞,小鼠眼表面上皮细胞主要表达TGF-β 2亚型。具体而言,我们证明了杯状细胞表达TGF-β 2的能力,并在培养物中响应Toll样受体4介导的刺激而增加TGF-β 2。杯状细胞不仅表达TGF-β 2,而且能够通过其细胞表面受体CD 36以血小板反应蛋白-1(TSP-1)依赖性方式激活TGF-β 2。此外,可能包括TGF-β 2的杯状细胞衍生的可溶性因子通过下调DC II类MHC和共刺激分子CD 80、CD 86和CD 40的表达将树突状细胞(DC)表型改变为致耐受性类型。因此,我们的研究表明杯状细胞作为眼粘膜中活性TGF-β 2的细胞来源,并暗示它们在维持粘膜免疫稳态中的免疫调节功能。
Goblet cells are secretory epithelial cells of mucosal tissues that confer protection from environmental agents or pathogens via expression and secretion of soluble mucins. Loss of these cells is associated with several chronic inflammatory disorders of the mucosa. Although demonstrated to transfer antigens from the luminal surface to stromal cells in the intestinal mucosa, it is not known if goblet cells contribute to the regulation of an immune response. In this study we report that similar to intestinal and respiratory mucosal epithelia, mouse ocular surface epithelia predominantly express the TGF-ß2 isoform. Specifically, we demonstrate the ability of goblet cells to express TGF-ß2 and increase it in response to Toll-Like Receptor 4 mediated stimulus in cultures. Goblet cells not only express TGF-ß2, but are also able to activate it in a thrombospondin-1 (TSP-1) dependent manner via their cell surface receptor CD36. Furthermore, goblet cell derived soluble factors that possibly include TGF-ß2, alter dendritic cell (DC) phenotype to a tolerogenic type by downregulating DC expression of MHC class II and co-stimulatory molecules CD80, CD86 and CD40. Thus our study demonstrates goblet cells as a cellular source of active TGF-ß2 in ocular mucosa and implicates their immunomodulatory function in maintaining mucosal immune homeostasis.
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