Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia

McCauley, Heather A.; Guasch, Géraldine

doi:10.1016/j.molmed.2015.06.003

Cited by 174 publications

(143 citation statements)

References 107 publications

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“…Studies on the transcriptional regulation of intestinal lineage determination have identified the factors controlling goblet cell differentiation and maturation (McCauley and Guasch, 2015). Notch1 signaling drives epithelial progenitor cell specification to absorptive enterocytes and inhibits secretory cell differentiation via the Hes1 transcription factor (Fre et al, 2005; Jensen et al, 2000), whereas Notch1 inhibition results in robust conversion of proliferating crypt progenitors into terminally differentiated goblet cells (van Es et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

Nowarski

Jackson

Gagliani

et al. 2015

Cell

463

361

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SUMMARY The intestinal mucosal barrier controlling the resident microbiome is dependent on a protective mucus layer generated by goblet cells, impairment of which is a hallmark of the inflammatory bowel disease Ulcerative Colitis. Here we show that IL-18 is critical in driving the pathologic breakdown of barrier integrity in a model of colitis. Deletion of Il18 or its receptor Il18r1 in intestinal epithelial cells (Δ/EC) conferred protection from colitis and mucosal damage in mice. In contrast, deletion of the IL-18 negative regulator Il18bp resulted in severe colitis associated with loss of mature goblet cells. Colitis and goblet cell loss were rescued in Il18bp−/−;Il18rΔ/EC mice, demonstrating that colitis severity is controlled at the level of IL-18 signaling in intestinal epithelial cells. IL-18 inhibited goblet cell maturation by regulating the transcriptional program instructing goblet cell development. These results inform on the mechanism of goblet cell dysfunction which underlies the pathology of Ulcerative Colitis.

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Section: Discussionmentioning

confidence: 99%

Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

Nowarski

Jackson

Gagliani

et al. 2015

Cell

463

361

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“…Data from the studies in the gut and respiratory tree laid the foundation for study of conjunctival epithelial and goblet cell differentiation. A very helpful review of similarities and differences between goblet cell differentiation in the mucosal systems was recently published (McCauley and Guasch, 2015). …”

Section: Goblet Cell Differentiationmentioning

confidence: 99%

Goblet cells of the conjunctiva: A review of recent findings

Gipson

2016

Progress in Retinal and Eye Research

193

127

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Goblet cells within the conjunctival epithelium are specialized cells that secrete mucins onto the surface of the eye. Recent research has demonstrated new characteristics of the cells, including factors influencing their differentiation, their gene products and their functions at the ocular surface. The following review summarizes the newly discovered aspects of the role of Spdef, a member of the Ets transcription factor family in conjunctival goblet cell differentiation, the newly discovered goblet cell products including claudin2, the Wnt inhibitor Frzb, and the transmembrane mucin Muc16. The current concepts of conjunctival goblet cell function, including debris removal and immune surveillance are reviewed, as are changes in the goblet cell population in ocular surface diseases. Major remaining questions regarding conjunctival cell biology are discussed.

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“…As goblet cells contribute to the maintenance of epithelium integrity, homeostasis, and modulation of immune responses (29,32,(39)(40)(41)(42)(43), the reduction in goblet cell numbers prompted us to determine whether HU alters intestinal barrier properties. We first examined the expression of one of the epithelial tight junction components, claudin 3, in the colon of HU and Ctrl mice.…”

Section: Altered Colonic Epithelial Cell Homeostasis In Hu Micementioning

confidence: 99%

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model

Shi

Wang

et al. 2017

FASEB j.

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Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HUlike epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model. FASEB J. 31, 3695-3709 (2017 Exposure to microgravity leads to alterations, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and immune dysfunction, in multiple systems (1). Limited reports also suggest that spaceflight and microgravity affect the integrity of intestinal epithelium. For instance, reduced length of villi and depth of crypts was found in rats that were flown on 12-d Cosmos 2044 and Foton M3 missions (2, 3), and decreased mucin production of intestinal epithelial cells was shown in rats that were flown on the 19.5-d Cosmos 605 mission (4). Colonic TGF-b expression was altered in mice aboard the 13-d STS-135 or 91-d International Space Station missions (5, 6). Using a well-accepted, ground-based spaceflight analog, the hindlimb unloading (HU) mouse model (7) found that simulated microgravity resulted in a transient increase in intestinal permeability, which is characterized by the elevation of circulating LPS and the activation of the innate immune system. The clinical significance and mechanism of these epithelial changes are not clear; however, Chopra et al. (8) reported that HU mice that were infected with Salmonella enterica serovar typhimurium had a 100-fold decrease in LD 50 compared with normal-gravity control (Ctrl) mice. This indicates that microgravity-induced intestinal epithelial changes may exacerbate bacte...

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Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia

Cited by 174 publications

References 107 publications

Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

Goblet cells of the conjunctiva: A review of recent findings

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model

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