Role of Goblet Cells in Intestinal Barrier and Mucosal Immunity

Abstract

Goblet cells and the mucus they secrete serve as an important barrier, preventing pathogens from invading the mucosa to cause intestinal inflammation. The perspective regarding goblet cells and mucus has changed, with current evidence suggesting that they are not passive but play a positive role in maintaining intestinal tract immunity and mucosal homeostasis. Goblet cells could obtain luminal antigens, presenting them to the underlying antigen-presenting cells (APCs) that induces adaptive immune responses. Various immunomodulatory factors can promote the differentiation and maturation of goblet cells, and the secretion of mucin. The abnormal proliferation and differentiation of goblet cells, as well as the deficiency synthesis and secretion of mucins, result in intestinal mucosal barrier dysfunction. This review provides an extensive outline of the signaling pathways that regulate goblet cell proliferation and differentiation and control mucins synthesis and secretion to elucidate how altering these pathways affects goblet functionality. Furthermore, the interaction between mucins and goblet cells in intestinal mucosal immunology is described. Therefore, the contribution of goblet cells and mucus in promoting gut defense and homeostasis is illustrated, while clarifying the regulatory mechanisms involved may allow the development of new therapeutic strategies for intestinal disorders.

Ellagic Acid Alleviates Oxidative Stress by Mediating Nrf2 Signaling Pathways and Protects against Paraquat-Induced Intestinal Injury in Piglets

“…In the present study, we also observed that EA administrations alleviated microvilli shedding and crypt hyperplasia, as well as increased the number of goblet cells in piglets injected with PQ, which is consistent with previous studies [ 51 ]. Oxidative stress can cause the intestinal barrier injury mainly manifested as villi shorting, crypt hyperplasia, and goblet cells apoptosis, which contribute further to a reduced ability for nutritional absorption and presentation of pathogens [ 62 , 63 ]. Maintaining intestinal integrity is a prerequisite to ensure the intestinal barrier function [ 64 ].…”

The Role of the Intestinal Epithelium in the “Weep and Sweep” Response during Gastro—Intestinal Helminth Infections

“…Being continually exposed to bacteria and parasites, mucus produced by the gut epithelium needs to be constantly renewed and recompositioned. This process stays under strict immune control (reviewed elsewhere [ 53 , 54 ]), however, regulation by Trefoil Factor Family proteins (TFFs) is worth mentioning due to the direct cooperation with another regulator of the immune response—amphiregulin—which is released in response to IL-33 by group 2 innate lymphoid cells (ILC2s) and protects tissue from damage [ 55 ] and facilitates worm expulsion [ 56 ]. Firstly, TFF3 enhances rheological mucus properties, improving barrier stability.…”

The Impact of MicroRNAs during Inflammatory Bowel Disease: Effects on the Mucus Layer and Intercellular Junctions for Gut Permeability

“…This could be attributed to the high turnover of epithelial cells in the colon, requiring a constant need for goblet cell differentiation and maturation, especially upon inflammation-induced tissue damage. The differentiation of goblet cells is controlled by a Notch-dependent pathway, and the terminal differentiation involves Krüppel-like transcription factor 4 (KLF4), growth factor independence 1 (GFI1) and SAM pointed domain-containing ETS transcription factor (SPDEF) [ 116 , 117 ]. Hath1, a basic helix–loop–helix transcription factor, is needed to counter the differentiation towards absorptive cell development [ 118 ].…”