Tuft cells in the pathogenesis of chronic rhinosinusitis with nasal polyps and asthma

Abstract

Tuft cells are a type of rare epithelial cell present in the respiratory and intestinal tracts, among other locations in humans, rodents, and reptiles.In addition to other functions, tuft cells use components of the taste transduction system to survey the extracellular environment and play a role in pathogen defense by stimulating neighboring ciliated epithelial cells to secrete antimicrobial products.The dominant epithelial source of interleukin-25 and an important source of cysteinyl leukotrienes in the airway, tuft cells have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis with nasal polyps and asthma.An important role of tuft cells is to act as a bridge between innate and adaptive immune responses in driving type 2 inflammation in the airway.Tuft cells cluster into subpopulations, which could play diverse roles in the pathophysiology of different diseases and possibly utilize immunomodulatory effector molecules outside of type 2 inflammatory cytokines.Further studies are needed, particularly on the use of better genetic tools for tracking tuft cell subpopulations to investigate the extent to which different subpopulations of tuft cells contribute to chronic inflammatory diseases.

Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection

“…This body of work supports vaginal epithelial cells to be the key source of IL-33-mediated type 2 immunity in the FGT during co-infection. Recent studies have identified myeloid sources of IL-33 to play roles in downregulating mucosal inflammation (Hung et al, 2020a(Hung et al, , 2020bJackson et al, 2020;Sell et al, 2020). The findings we present here do not currently suggest a role for cells other than epithelial cells as a contributing source of IL-33.…”

Taste receptor T1R3 in nasal cilia detectsStaphylococcus aureusD-amino acids to increase apical glucose uptake and enhance innate immunity

“…SCCs appear to be regulated by type II cytokines like IL-13 or IL-4 and/or exposure to fungal metabolites. (16) Thus, SCCs may only be prevalent in the nose of CRS patients with nasal polyps (CRSwNP), a subset of CRS driven by type II cytokines, (70) or in patients with allergic fungal sinusitis. CRS without ( sans ) nasal polyps (CRSsNP) is most often characterized by other inflammatory profiles.…”

“…These cells are also referred to as “brush cells.” (15) SCCs regulate several responses, including IL-25 and/or acetylcholine release to activate epithelial inflammation or trigger mucus clearance, respectively. (16, 17) In the nose, they also regulate secretion of antimicrobial peptides like defensins. (13, 18) SCC activation of antimicrobial peptide secretion is reduced by activation of the sweet taste receptor (taste family 1 receptor) subunits T1R2 and T1R3 via ASL glucose (13) or sweet bacterial D-amino acids.…”

Nicotinic acetylcholine receptor signaling maintains epithelial barrier integrity

“…The endogenous ligand of nAchR, acetylcholine (Ach), is a classic neurotransmitter synthesized by Choline Acetyltransferase (ChAT) in cholinergic neurons, as well as in immune cells and epithelial cells, such as brush/tuft cells (Kummer & Krasteva-Christ, 2014; Wessler & Kirkpatrick, 2008). Such cells orchestrate type 2 inflammatory responses (O’Leary et al, 2019; Sell et al, 2021), mucociliary clearance (Perniss et al, 2020) and limit biliary inflammation (O’Leary et al, 2022; O’Leary et al, 2019). How Ach influences homeostasis of barrier epithelia and how disease-associated nAchR variants perturb epithelial function remains mostly unclear.…”