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Review
. 2021 Jul 13:14:3171-3183.
doi: 10.2147/JIR.S318327. eCollection 2021.

Role of Goblet Cells in Intestinal Barrier and Mucosal Immunity

Songwei Yang  1 , Min Yu  2
Affiliations
Review

Role of Goblet Cells in Intestinal Barrier and Mucosal Immunity

Songwei Yang et al. J Inflamm Res. .

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.

Keywords: Mucin2; cytokine; goblet cell; intestinal barrier; intestinal tract; mucosal immunity.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Role of transcription factors in goblet cell differentiation.
Figure 2
Figure 2
Schematic representation of the promoter regions of MUC2.
Figure 3
Figure 3
Regulatory mechanism of mucus secretion in goblet cell and interaction with immune cells. Soluble antigens in the lumen of the intestine such as LPS and P3CSK4 are endocytosed by senGC, triggering TLR-MyD88 signaling, ROS synthesis and NLRP6 inflammasome, causing Ca2+-dependent secretion of MUC2. Goblet cells can also deliver luminal antigens to APCs, initiating adaptive responses.
Figure 4
Figure 4
Immune regulation of goblet cell function and mucin production. (1) IL-33 and IL-25 activate ILC2 and Th2 cells during parasite infections, which release Th2 cytokines such as IL-4, IL-5, IL-9, and IL-13. IL-4 and IL-13 can promote goblet cell proliferation through STAT6 signaling. IL-4 and IL-13 also upregulate the expression of TFF3 and MUC2 via STAT6 or MAPK signaling. IL-25 and IL-9 also promoted goblet cell proliferation and mucin expression through IL-13 dependent pathway. IL-33 induces goblet cell differentiation by stimulating ILCs to produce IL-13. (2) Th1 cytokines such as TNF-α, IL-1β and IFN-γ play complex way in regulating mucin biosynthesis, which not only induce, but also inhibit MUC2 expression in different pathophysiological conditions. (3) IL-22 can regulate goblet cell differentiation and induces mucin expression in STAT3 signaling. IL-10 promotes mucin expression by inhibiting protein misfolding and ER stress in goblet cells.
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