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

Contreras-Ruiz L, Masli S - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Goblet cells deficient in TSP-1 or CD36 fail to release active TGF-ß2.Activation of TGF-ß2 by LPS-exposed WT, TSP-1 deficient or CD36 −/− cultured conjunctival goblet cells was assessed using MFB-F11 reporter cell line. Unlike WT, both TSP-1 and CD36 deficient goblet cells failed to increase their active TGF-ß2 in response to LPS exposure in culture. Changes in the levels relative to the untreated goblet cells are presented. (*P < 0.05 compared to WT)
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pone.0120284.g005: Goblet cells deficient in TSP-1 or CD36 fail to release active TGF-ß2.Activation of TGF-ß2 by LPS-exposed WT, TSP-1 deficient or CD36 −/− cultured conjunctival goblet cells was assessed using MFB-F11 reporter cell line. Unlike WT, both TSP-1 and CD36 deficient goblet cells failed to increase their active TGF-ß2 in response to LPS exposure in culture. Changes in the levels relative to the untreated goblet cells are presented. (*P < 0.05 compared to WT)

Mentions: To determine if the membrane colocalization of TSP-1, CD36, and TGF-ß2 is essential for the TGF-ß2 activation by goblet cells, we evaluated the ability of TSP-1 or CD36 deficient goblet cells to activate their TGF-ß2. We first confirmed by real-time PCR that all the three tested goblet cells (WT, TSP-1−/− and CD36−/−) express comparable levels of TGF-ß2 message upon their LPS exposure (WT: 1.6 ± 0.1; TSP-1−/−: 1.4 ± 0.1; CD36−/− 2.1 ± 0.1 fold increase over untreated). We then tested active TGF-ß2 content of their supernatants using MFB-F11 reporter cells. Unlike WT goblet cells that responded to LPS-exposure with over 10-fold increase in secreted active TGF-ß2, both TSP-1 and CD36 deficient goblet cells failed to increase their active TGF-ß2 secretion in response to LPS exposure in culture (Fig. 5). Thus our results indicate that conjunctival goblet cells indeed depend on TSP-1 to activate their own TGF-ß2.


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

Contreras-Ruiz L, Masli S - PLoS ONE (2015)

Goblet cells deficient in TSP-1 or CD36 fail to release active TGF-ß2.Activation of TGF-ß2 by LPS-exposed WT, TSP-1 deficient or CD36 −/− cultured conjunctival goblet cells was assessed using MFB-F11 reporter cell line. Unlike WT, both TSP-1 and CD36 deficient goblet cells failed to increase their active TGF-ß2 in response to LPS exposure in culture. Changes in the levels relative to the untreated goblet cells are presented. (*P < 0.05 compared to WT)
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368435&req=5

pone.0120284.g005: Goblet cells deficient in TSP-1 or CD36 fail to release active TGF-ß2.Activation of TGF-ß2 by LPS-exposed WT, TSP-1 deficient or CD36 −/− cultured conjunctival goblet cells was assessed using MFB-F11 reporter cell line. Unlike WT, both TSP-1 and CD36 deficient goblet cells failed to increase their active TGF-ß2 in response to LPS exposure in culture. Changes in the levels relative to the untreated goblet cells are presented. (*P < 0.05 compared to WT)
Mentions: To determine if the membrane colocalization of TSP-1, CD36, and TGF-ß2 is essential for the TGF-ß2 activation by goblet cells, we evaluated the ability of TSP-1 or CD36 deficient goblet cells to activate their TGF-ß2. We first confirmed by real-time PCR that all the three tested goblet cells (WT, TSP-1−/− and CD36−/−) express comparable levels of TGF-ß2 message upon their LPS exposure (WT: 1.6 ± 0.1; TSP-1−/−: 1.4 ± 0.1; CD36−/− 2.1 ± 0.1 fold increase over untreated). We then tested active TGF-ß2 content of their supernatants using MFB-F11 reporter cells. Unlike WT goblet cells that responded to LPS-exposure with over 10-fold increase in secreted active TGF-ß2, both TSP-1 and CD36 deficient goblet cells failed to increase their active TGF-ß2 secretion in response to LPS exposure in culture (Fig. 5). Thus our results indicate that conjunctival goblet cells indeed depend on TSP-1 to activate their own TGF-ß2.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus