**3.3 Goblet cells**

*Advances in Poultry Nutrition Research*

epithelial cells.

**3.2 Trefoil factors**

mon unit is the trefoil motif [25].

between TFF and the immune system.

luminal insults [25, 28, 29].

electrochemical properties of mucopolysaccharides are believed to determine the

Mucins have a key role in avoiding potential damage from microbes. The mechanism by which mucus controls microflora colonization is referred to as part of innate epithelial cells [19]. The role of mucin on microbe colonization is manifested in at least two distinct ways. First, some microbes are mucolytic, including Bacteroidetes, and use mucin glycoproteins and carbohydrates as an energy source and provide physical support for intestinal colonization. Moreover, these bacteria provide substrates for other bacteria in the outer mucus layer by degrading the mucins [20, 21]. Second, mucins are generally "toxic" to the proliferation of certain microbes. Mucus gel inhibits proliferation by entrapping microbes that are starved or killed by antimicrobial peptides, and/or expulsed by the luminal flow. Mucus also provides a physicochemical barrier to prevent microbes from direct contact with

Moreover, the mucus gel provides a matrix for antimicrobial molecules, which are mainly produced by Paneth cells. Direct interactions with mucins can facilitate the diffusion of these antimicrobial molecules [22]. Taken together, mucins have been proposed to play an important role in shaping microbial communities at the intestinal mucosa. Recent studies suggest the correlation between changes in mucin glycosylation profile and deviations of overall microbial community ecology as well

Co-expressed with mucin-secreting cells and in close relation with mucus, trefoil factors (TFF) demonstrate an interesting group of mucus molecules. Trefoil factors were initially discovered in the pig pancreas [25] and further characterization of this family has strikingly observed their abundant expression in the GIT and their efficacy as therapeutics especially for preventing and treating various GIT conditions [26, 27]. They are named as trefoil by their "three-leaf" structure and are a family of small (7-12 kDa in mammals) protease resistant peptides whose com-

It is now clear that TFF participate in the healing of mucosal injury in disease conditions by promoting cell migration over damaged areas (rather than promoting cell division), and inhibiting cell death, and are also believed to be involved in physiological repair of epithelia from daily apical sloughing against frequent

TFF have recently been found to participate in immune responses. It was showed

TFF are thought to cooperatively interact with mucins in the lumen to enhance the protective barrier properties of the adherent mucus layer against bacterial and toxic insults [25, 28]. Thim et al. [33] observed significant increase in the viscosity and elasticity of gastric mucin solutions because of TFF2 addition [33]. Increased viscosity could help prevent antigens from approaching the epithelium surface, especially in healing epithelia, which eventually benefits epithelium restitution and

that TFF2 deficiency or administration of recombinant TFF2 altered the expression of immune associated genes including defensin genes in Paneth cells [30]. The presence of TFF in immune organs, including spleen, thymus, lymph nodes and bone marrow [31], may suggest possible regulatory role(s) played there. TFF can be a potent mitogen by regulating chemotaxis, stimulating the migration of immune cells. The molecular basis of such may be supported by the recent in vitro evidence that recombinant TFF2 activates CXCR4 chemokine receptors and attenuates CXCR4 mediated chemotaxis [32]. This finding also highlights a molecular linkage

chemical and biophysical characteristics of mucus along the GIT [18].

as altered abundances of specific microbes [23, 24].

**122**

Goblet cells together with absorptive enterocytes, Paneth cells (secreting antimicrobial peptides etc.) and enteroendocrine cells, represent the four principal cell types that are continuously renewed in the epithelium of the small intestine. During intestinal epithelial cell regeneration, pluripotent stem cells that reside at the bottom of the crypt divide to generate multiple cell lineages which migrate from the proliferative crypts to the villus tip [34]. While migrating along the crypt-to-villus axis, goblet cells are terminally differentiated from secretory cell lineage derived from a common Math1-expresing progenitor cell [35]. Goblet cell differentiation is controlled by winged helix transcription factors Foxa1/a2 which can also transactivate Muc2 promoters [36].

It is generally believed that goblet cells producing neutral mucins contain little sialic acid and represent an immature state; while goblet cells containing acidic mucins are more likely resistant to infections because they are normally "upregulated" in response to bacterial infection. In addition to mucins, several other molecules are co-expressed within the intestine such as ingobsin (localized in human and rat goblet cells) with endoproteolytic activity in the presence of both epidermal growth factor and cobalamin-binding protein haptocorrin [37]. TFFs are (specifically TFF3) along with mucins biomarkers of goblet cells.
