Regulation of Intestinal Stem Cell Stemness by the Aryl Hydrocarbon Receptor and Its Ligands

Abstract

Maintenance of intestinal homeostasis requires the integration of immunological and molecular processes together with environmental, diet, metabolic and microbial cues. Key to this homeostasis is the proper functioning of epithelial cells originating from intestinal stem cells (ISCs). While local factors and numerous molecular pathways govern the ISC niche, the conduit through which these processes work in concordance is the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, whose role in immunoregulation is critical at barrier surfaces. In this review, we discuss how AhR signaling is emerging as one of the critical regulators of molecular pathways involved in epithelial cell renewal. In addition, we examine the putative contribution of specific AhR ligands to ISC stemness and epithelial cell fate.

A Novel Probiotic Bacillus subtilis Strain Confers Cytoprotection to Host Pig Intestinal Epithelial Cells during Enterotoxic Escherichia coli Infection

“…Maintenance of intestinal epithelial homeostasis is strictly regulated by cellular proliferation in the crypt and apoptotic cell shedding from villus tip. The cell migration from the base of the crypt to the apical epithelial surface sustains matured cell turnover by maintaining rigorous equilibrium between cell death and cell proliferation ( 42 , 89 ). Increased intestinal cell apoptosis and shedding have been observed in pathological states leading to inflammation led colitis ( 42 , 90 – 92 ).…”

Stem-Cell Theory of Cancer: Implications for Antiaging and Anticancer Strategies

“…AHR is a regulator of cytochrome P450, which metabolizes xenobiotic chemicals coming through our alimentary canal. Importantly, AHR displays stemness properties and dispenses stem-like functions because it regulates metabolic enzymes, moderates immunity, and balances stem cell pluripotency vs differentiation [ 50 , 51 ]. After all, AHR binds exogenous ligands, such as natural plant flavonoids, polyphenols, and indoles, that we ingest to feed ourselves, as well as to feed the microbiome in our guts.…”

Cell fate‐inducing CARs orthogonally control multiple signaling pathways

“…Cell fates are regulated by a variety of receptors expressed on the cell membrane or in the cytosol. [ 1–3 ] Among the receptors, transmembrane receptors receive the specific ligands in the extracellular domain, undergo conformational changes, and activate downstream signaling pathways to control cell fates. [ 4–6 ] Thus, transmembrane receptors play important roles in responding to extracellular signals to adapt cells to extracellular environmental changes through intracellular signal transduction.…”

“…Cell fates are regulated by a variety of receptors expressed on the cell membrane or in the cytosol. [1][2][3] Among the receptors, transmembrane receptors receive the specific ligands in the extracellular domain, undergo conformational changes, and activate downstream signaling ABBREVIATIONS: aiCAR, apoptosis-inducing CAR; CAR, chimeric antigen receptor; cfiCAR, cell fate-inducing CAR; DNP, dinitrophenol; FL, fluorescein; IL-3, interleukin-3; IRES, internal ribosomal entry site; JAK, Janus kinase; JNK, c-Jun N-terminal kinase; piCAR, proliferation-inducing CAR; RANK, receptor activator of nuclear factor κB; scFv, single-chain Fv; STAT, signal transducers and activators of transcription pathways to control cell fates. [4][5][6] Thus, transmembrane receptors play important roles in responding to extracellular signals to adapt cells to extracellular environmental changes through intracellular signal transduction.…”