Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine

Xiong, Ze; Zhu, Xiaoxiao; Geng, Jingjing; Xu, Yu; Wu, Runyuan; Cun-zhen, LI; Fan, Dongdong; Qin, Xiwen; Du, Youwei; Tian, Yong; Fan, Zusen

doi:10.1016/j.immuni.2022.03.001

Cited by 41 publications

(24 citation statements)

References 48 publications

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“…According to a single-cell survey of the small intestinal epithelium, tuft cells show several specific G protein-coupled receptors, such as the sweet taste receptor type 1 member 3, bitter taste receptors type 2, succinate receptor 1, and FFAR3 [24]. Recent studies have revealed that activating taste receptors or the Sucnr1 signaling pathway can enhance tuft cell hyperplasia and induce tuft cells to release IL-25, thus initiating type 2 immunity in the gut [33,[57][58][59], and Vmn2r26 in tuft cells mediates the recognition of bacterial metabolites, thus helping to eradicate bacteria [60]. However, the role of FFAR3 in tuft cells has not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Indolepropionic acid reduces obesity‐induced metabolic dysfunction through colonic barrier restoration mediated via tuft cell‐derived IL‐25

et al. 2022

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Previous studies have indicated that indolepropionic acid (IPA), derived from dietary tryptophan via gut microbiota conversion, is negatively correlated with type 2 diabetes mellitus and systemic low-grade inflammation. However, the effects of IPA administration on obesity, as well as the underlying mechanisms, remain unclear. In the present study, we observed that obesity leads to a dramatic reduction in IPA levels in both the serum and colonic mucosa, and IPA supplementation exerted beneficial effects on weight, as well as on glucose and lipid metabolism disorders. In adipose tissue, IPA treatment had no direct effect on adipocyte differentiation, but it significantly ameliorated adipose inflammation, thus preventing adipocyte enlargement. Moreover, IPA administration promoted gut integrity, increased the expression of tight junction proteins, and downregulated colonic inflammation; these effects were demonstrated to have a poor relationship with gut microbiota composition. Mechanistically, IPA significantly promoted the expansion of the tuft cell lineage in the gut and increased the secretion of interleukin-25 both in vivo and ex vivo, which contributes to the integrity of the gut barrier. This may partly depend on the free fatty acid receptor 3 pathway in tuft cells. Overall, our results demonstrate that IPA supplementation prevents the development of highfat diet-induced obesity and metabolic disorders by restoring tuft cellinterleukin-25-mediated colonic barrier integrity; hence, IPA could be a potential agent for treatment of obesity.

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Section: Discussionmentioning

confidence: 99%

Indolepropionic acid reduces obesity‐induced metabolic dysfunction through colonic barrier restoration mediated via tuft cell‐derived IL‐25

et al. 2022

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“…LTE 4 enhances the ability of PGD 2 to induce ILC2 and Th2 cells ( 52 , 67 ), implying a synergistic role of the two mast cell-derived eicosanoids in promoting type 2 immunity. Activation of cPLA 2 α in intestinal tuft cells leads to generation of not only LTC 4 (see above) but also PGD 2 , the latter of which increases mucus secretion by goblet cells to impede pathogen invasion ( 68 ). Thus, it seems that mast cells and tuft cells share common characteristics in that they produce both PGD 2 (via the cPLA 2 α/COX-2/H-PGDS pathway) and LTC 4 (via the cPLA 2 α/5-LOX/LTC 4 S pathway) in response to specific stimuli and participate in fine-tuning allergic responses as well as host defense against pathogens.…”

Section: Regulatory Roles Of Intracellular Pla 2 S...mentioning

confidence: 99%

Regulatory Roles of Phospholipase A2 Enzymes and Bioactive Lipids in Mast Cell Biology

Taketomi

Murakami

2022

Front. Immunol.

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Lipids play fundamental roles in life as an essential component of cell membranes, as a major source of energy, as a body surface barrier, and as signaling molecules that transmit intracellular and intercellular signals. Lipid mediators, a group of bioactive lipids that mediates intercellular signals, are produced via specific biosynthetic enzymes and transmit signals via specific receptors. Mast cells, a tissue-resident immune cell population, produce several lipid mediators that contribute to exacerbation or amelioration of allergic responses and also non-allergic inflammation, host defense, cancer and fibrosis by controlling the functions of microenvironmental cells as well as mast cell themselves in paracrine and autocrine fashions. Additionally, several bioactive lipids produced by stromal cells regulate the differentiation, maturation and activation of neighboring mast cells. Many of the bioactive lipids are stored in membrane phospholipids as precursor forms and released spatiotemporally by phospholipase A2 (PLA2) enzymes. Through a series of studies employing gene targeting and lipidomics, several enzymes belonging to the PLA2 superfamily have been demonstrated to participate in mast cell-related diseases by mobilizing unique bioactive lipids in multiple ways. In this review, we provide an overview of our current understanding of the regulatory roles of several PLA2-driven lipid pathways in mast cell biology.

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“…Recently, tuft cells were divided into two groups [ 43 , 47 ]. Tuft-1 cells share very similar transcriptomic features with type II TRCs in taste buds, whereas tuft-2 cells show enrichment for immune-related genes [ 43 , 55 ]. Taste receptors and their downstream effectors are generally expressed in tuft-1 cells.…”

Section: Categorizing Ectopic Taste Receptor Expressionmentioning

confidence: 99%

“…Intestinal tuft cells are crucial for defense against microbial challenges because they detect microbe-derived chemicals in the intestinal lumen. Upon activation, these tuft cells secrete interleukin 25 (IL-25) to drive the activation of type 2 innate lymphoid cells 2 (ILC2) [ 40 , 42 , 44 , 55 , 58 ]. Multiple research groups found that intestinal tuft cells exhibit a transcriptional repertoire similar to type II TRCs.…”

Section: Categorizing Ectopic Taste Receptor Expressionmentioning

confidence: 99%

Taste Receptors beyond Taste Buds

Jeong

2022

IJMS

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Taste receptors are responsible for detecting their ligands not only in taste receptor cells (TRCs) but also in non-gustatory organs. For several decades, many research groups have accumulated evidence for such “ectopic” expression of taste receptors. More recently, some of the physiologic functions (apart from taste) of these ectopic taste receptors have been identified. Here, we summarize our current understanding of these ectopic taste receptors across multiple organs. With a particular focus on the specialized epithelial cells called tuft cells, which are now considered siblings of type II TRCs, we divide the ectopic expression of taste receptors into two categories: taste receptors in TRC-like cells outside taste buds and taste receptors with surprising ectopic expression in completely different cell types.

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Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine

Cited by 41 publications

References 48 publications

Indolepropionic acid reduces obesity‐induced metabolic dysfunction through colonic barrier restoration mediated via tuft cell‐derived IL‐25

Indolepropionic acid reduces obesity‐induced metabolic dysfunction through colonic barrier restoration mediated via tuft cell‐derived IL‐25

Regulatory Roles of Phospholipase A2 Enzymes and Bioactive Lipids in Mast Cell Biology

Taste Receptors beyond Taste Buds

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