Contreras-Ruiz Laura, Masli Sharmila
Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
PLoS One. 2015 Mar 20;10(3):e0120284. doi: 10.1371/journal.pone.0120284. eCollection 2015.
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.
杯状细胞是黏膜组织中的分泌性上皮细胞，通过表达和分泌可溶性黏蛋白来抵御环境因子或病原体。这些细胞的缺失与多种黏膜慢性炎症性疾病相关。尽管已证明杯状细胞可将肠黏膜腔表面的抗原传递给基质细胞，但尚不清楚杯状细胞是否参与免疫反应的调节。在本研究中，我们报告，与肠道和呼吸道黏膜上皮类似，小鼠眼表上皮主要表达转化生长因子β2（TGF-β2）亚型。具体而言，我们证明了杯状细胞表达TGF-β2的能力，并在培养物中对Toll样受体4介导的刺激作出反应而增加其表达。杯状细胞不仅表达TGF-β2，还能够通过其细胞表面受体CD36以血小板反应蛋白-1（TSP-1）依赖的方式激活它。此外，杯状细胞衍生的可溶性因子（可能包括TGF-β2）通过下调树突状细胞（DC）主要组织相容性复合体II类分子以及共刺激分子CD80、CD86和CD40的表达，将DC表型改变为致耐受性类型。因此，我们的研究证明杯状细胞是眼黏膜中活性TGF-β2的细胞来源，并暗示了它们在维持黏膜免疫稳态中的免疫调节功能。
