Tuft cell

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3D image of mouse jejunum tuft cells : A free-floating cryosection was immunostained with a tuft cell marker (anti-phospho-specific antibody against Girdin tyrosine-1798; pY1798 antibody from Immuno-Biological Laboratories) following an established method (Kuga D et al. Journal of Histochemistry & Cytochemistry 65(6) 347-366, Mizutani Y et al. Journal of Visualized Experiments (133) e57475). SAMPLE: Cryosectioned free-floating DDY mouse jejunum (green: phospho-Girdin at tyrosine 1798, red: phalloidin, blue: DAPI) prepared by Iida M, Tanaka M, Asai M in Institute for Developmental Research, Aichi Human Service Center (Kasugai Japan). 3D-video edited by Ito T (Nikon Instech Japan). MICROSCOPE: NIKON A1R-TiE. OBJECTIVE LENS: Plan Apo λ 60x Oil.

Tuft cells are chemosensory cells in the epithelial lining of the intestines. Similar tufted cells are found in the respiratory epithelium where they are known as brush cells. [1] The name "tuft" refers to the brush-like microvilli projecting from the cells. Ordinarily there are very few tuft cells present but they have been shown to greatly increase at times of a parasitic infection. [2] Several studies have proposed a role for tuft cells in defense against parasitic infection. In the intestine, tuft cells are the sole source of secreted interleukin 25 (IL-25). [3] [4] [5]

Contents

ATOH1 is required for tuft cell specification but not for maintenance of a mature differentiated state, and knockdown of Notch results in increased numbers of tuft cells. [5]

Human tuft cells

The human gastrointestinal (GI) tract is full of tuft cells for its entire length. These cells were located between the crypts and villi. On the basal pole of all cells was expressed DCLK1. They did not have the same morphology as was describe in animal studies but they showed an apical brush border the same thickness. Colocalization of synaptophysin and DCLK1 were found in the duodenum, this suggests that these cells play a neuroendocrine role in this region. A specific marker of intestinal tuft cells is microtubule kinase - Double cortin-like kinase 1 (DCLK1). Tuft cells that are positive in this kinase are important in gastrointestinal chemosensation, inflammation or can make repairs after injuries in the intestine. [6]

Function

One key to understanding the role of tuft cells is that they share many characteristics with chemosensory cells in taste buds. For instance, they express many taste receptors and taste signaling apparatus. This might suggest that tuft cells could function as chemoreceptive cells that can sense many chemical signals around them. However, with more new research suggests that tuft cells can also be activated by the taste receptor apparatus. These can also be triggered by different small molecules, such as succinate and aeroallergens. Tuft cells have been known to secrete various molecules which are important for biological functions. Due to this, tuft cells act as danger sensors and trigger a secretion of biologically active mediators. Despite this, the signals and the mediators that they secrete are wholly dependent on context. For example, tuft cells that are in the urethra respond to bitter compounds, through activation of the taste receptor. This then results in a rise in intracellular Ca2+  and the release of acetylcholine. It is thought that this then triggers an activation of various other cells in the proximity which then leads to bladder detrusor reflex and a greater emptying of the bladder. [7]

Tuft cells in type-2 immunity

It has been discovered that the tuft cells in the intestines of mice are activated by parasitic infections. This leads to a secretion of IL25. IL25, being the key activator of innate lymphoid cells type 2. This then initiates and amplifies type-2 cytokine response, characterized by secretion of cytokines from ILC2 cells. [7] Tissue remodeling during type-2 immune response is based on cytokine interleukin (IL)-13. This interleukin is produced mainly by group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2s) located in lamina propria. Also during worm infection, the amount of tuft cells dramatically rises. Hyperplasia of tuft cells and goblet cells is a hallmark of type 2 infection and is regulated by a feed-forward signalling circuit. IL-25 produced by tuft cells induces IL-13 production by ILC2s in the lamina propria. IL-13 then interact with uncommitted epithelial progenitors to affect their lineage selection toward goblet and tuft cells. As a result, the IL-13 is responsible for dramatic remodeling enterocyte epithelium to epithelium which are dominated by tuft and goblet cells. Without IL-25 from tuft cells worm clearance is delayed. The type-2 immune response is based on tuft cells and the response is severely reduced without the presence of these cells, which confirm the important physiologic function for these cells during worm infection. [8] Activation of Th2 cells is an important part of this feed-forward loop. The activation of tuft cells in the intestine is connected with metabolite succinate, which is produced by a parasite and binds to the specific tuft cells receptor Sucnr1 on their surface. Also, the role of intestinal tuft cells can be important for local regeneration in the intestine after an infection. [7]

Morphology

Tuft cells were identified for the first time in the trachea and gastrointestinal tract in rodent, due to their typical morphology, by electron microscopy. The characteristic tubulovesicular system and apical bundle of microfilaments which are connected to tuft by long and thick microvilli, reaching into the lumen, gave them their name. [1] This figure gave these cells their name and the whole of tufted morphology. The distribution and size of tuft cell microvilli are very different from enterocytes that neighbour them. Also tuft cells, in comparison with enterocytes, do not have a terminal web at the base of apical microvilli. [9] Other characteristics of tuft cells are: quite narrow apical membrane which cause the tuft cells to be viewed as pinched at the top, prominent microfilaments from actin which extend to the cell and finish just above the nucleus, vast but largely empty apical vesicles which make a tubulovesicular network, on the apical side of the cells' nucleus is a Golgi apparatus, deficiency of rough endoplasmic reticulum and desmosomes with tight junction which fixes tuft cells to their neighbours. [8] The shape of the tuft cell body varies and depends on the organ. Tuft cells in the intestine are cylindric and narrow at the apical and basal ends. Alveolar tuft cells are flatter in comparison with intestinal and gall bladder tuft cells have a cuboidal shape. Differences in tuft cells can reflect their organ's specific functions. Tuft cells express chemosensory proteins, like TRPM5 and α-gustducin. These proteins indicate that neighbouring neurons can innervate tuft cells. [9]

Tuft cells can be identified by staining for cytokeratin 18, neurofilaments, actin filaments, acetylated tubulin, and DCLK1 to differentiate between tuft cells and enterocytes. [5]

Tuft cells are found in the intestine, and stomach, and as pulmonary brush cells in the respiratory tract, from nose to alveoli. [10]

Tuft cells in disease

A loss of tolerance to antigens that appear in the environment cause inflammatory bowel disease (IBD) and Crohn's disease (CD) in people who are more genetically susceptible. Helminth colonization inducts a type-2 immune response, causes mucosal healing and achieves clinical remission. During an intense infection, tuft cells can make their own specification and the hyperplasia of tuft cells is a key response to the expulsion of the worm. This shows that the modulation of tuft cell function may be effective in the treatment of Crohn's Disease. [11]

Helminth infections

Tuft cells have been shown to use taste receptors in the detection of many different helminth species. The clearance of helminth in mice that lacked taste receptor function (Trpm5 or/-gustducin  KO)   or enough tuft cells (Pou2f3 KO) was impaired compared to that of wild-type mice. This shows that tufts cells are important in playing a protective role during the helminth infections. It was observed that IL-25 derived from tuft cells was mediating the protective response, initiating type 2 immune responses. [12]

History and distribution

Tuft cells were first discovered in the trachea of the rat, and in the mouse stomach. [5]

In the late 1920s, Dr. Chlopkov was tracking a project on developmental stages of goblet cells which are in the intestines. In the microscope he found a cell with a bundle of unusually long microvilli rising into the intestinal lumen. He thought he had found an early stage intestinal goblet cell but it was actually the first report of a new epithelial lineage which we now call the tuft cell. In 1956, two scientists, Rhodin and Dalhamn, described tuft cells in the rat trachea; later the same year Järvi and Keyriläinen found similar cells in the mouse stomach. [8]

Tuft cells are generally located in the columnar epithelium organs derived from endoderm. In rodents, they have been definitively been found: for example, in the trachea, the thymus, the glandular stomach, the gall bladder, the small intestine, the colon, the auditory tube, the pancreatic duct and the urethra. Tuft cells are most of the time isolated cells and take <1% of the epithelium. In the mouse gall bladder and rat bile and pancreatic duct, the tuft cells are more abundant but still isolated. [8]

See also

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<span class="mw-page-title-main">Microvillus</span> Microscopic protrusion of a cell membrane that increases surface area substantially

Microvilli are microscopic cellular membrane protrusions that increase the surface area for diffusion and minimize any increase in volume, and are involved in a wide variety of functions, including absorption, secretion, cellular adhesion, and mechanotransduction.

<span class="mw-page-title-main">Intestinal villus</span> Finger-like projection of the small intestine

Intestinal villi are small, finger-like projections that extend into the lumen of the small intestine. Each villus is approximately 0.5–1.6 mm in length, and has many microvilli projecting from the enterocytes of its epithelium which collectively form the striated or brush border. Each of these microvilli are about 1 µm in length, around 1000 times shorter than a single villus. The intestinal villi are much smaller than any of the circular folds in the intestine.

<span class="mw-page-title-main">Enterocyte</span> Type of intestinal cell

Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its surface area. This facilitates transport of numerous small molecules into the enterocyte from the intestinal lumen. These include broken down proteins, fats, and sugars, as well as water, electrolytes, vitamins, and bile salts. Enterocytes also have an endocrine role, secreting hormones such as leptin.

<span class="mw-page-title-main">Goblet cell</span> Epithelial cells that secrete mucins

Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their secretions, when under stress. The term goblet refers to the cell's goblet-like shape. The apical portion is shaped like a cup, as it is distended by abundant mucus laden granules; its basal portion lacks these granules and is shaped like a stem.

Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.

<span class="mw-page-title-main">Interleukin 13</span> Protein and coding gene in humans

Interleukin 13 (IL-13) is a protein that in humans is encoded by the IL13 gene. IL-13 was first cloned in 1993 and is located on chromosome 5q31.1 with a length of 1.4kb. It has a mass of 13 kDa and folds into 4 alpha helical bundles. The secondary structural features of IL-13 are similar to that of Interleukin 4 (IL-4); however it only has 25% sequence identity to IL-4 and is capable of IL-4 independent signaling. IL-13 is a cytokine secreted by T helper type 2 (Th2) cells, CD4 cells, natural killer T cell, mast cells, basophils, eosinophils and nuocytes. Interleukin-13 is a central regulator in IgE synthesis, goblet cell hyperplasia, mucus hypersecretion, airway hyperresponsiveness, fibrosis and chitinase up-regulation. It is a mediator of allergic inflammation and different diseases including asthma.

<span class="mw-page-title-main">Paneth cell</span> Anti-microbial epithelial cell of the small intestine

Paneth cells are cells in the small intestine epithelium, alongside goblet cells, enterocytes, and enteroendocrine cells. Some can also be found in the cecum and appendix. They are located below the intestinal stem cells in the intestinal glands and the large eosinophilic refractile granules that occupy most of their cytoplasm.

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<span class="mw-page-title-main">Intestinal gland</span> Gland between the intestinal villi that produces new cells

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<span class="mw-page-title-main">Respiratory epithelium</span> Mucosa that serves to moisten and protect the airways

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Microfold cells are found in the gut-associated lymphoid tissue (GALT) of the Peyer's patches in the small intestine, and in the mucosa-associated lymphoid tissue (MALT) of other parts of the gastrointestinal tract. These cells are known to initiate mucosal immunity responses on the apical membrane of the M cells and allow for transport of microbes and particles across the epithelial cell layer from the gut lumen to the lamina propria where interactions with immune cells can take place.

<span class="mw-page-title-main">Intraepithelial lymphocyte</span>

Intraepithelial lymphocytes (IEL) are lymphocytes found in the epithelial layer of mammalian mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract. However, unlike other T cells, IELs do not need priming. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT).

<span class="mw-page-title-main">Taste receptor</span> Type of cellular receptor that facilitates taste

A taste receptor or tastant is a type of cellular receptor which facilitates the sensation of taste. When food or other substances enter the mouth, molecules interact with saliva and are bound to taste receptors in the oral cavity and other locations. Molecules which give a sensation of taste are considered "sapid".

<span class="mw-page-title-main">Intestinal epithelium</span> Single-cell layer lining the intestines

The intestinal epithelium is the single cell layer that form the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelial cells, it serves two main functions: absorbing useful substances into the body and restricting the entry of harmful substances. As part of its protective role, the intestinal epithelium forms an important component of the intestinal mucosal barrier. Certain diseases and conditions are caused by functional defects in the intestinal epithelium. On the other hand, various diseases and conditions can lead to its dysfunction which, in turn, can lead to further complications.

<span class="mw-page-title-main">Mucosal immunology</span> Field of study

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<span class="mw-page-title-main">Plastin</span>

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<span class="mw-page-title-main">Intestinal mucosal barrier</span>

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<span class="mw-page-title-main">De'Broski R. Herbert</span> American immunologist

De’Broski. R. Herbert is an immunologist, parasitologist, academic, and biomedical researcher. He is currently Full Professor of Immunology, and Penn Presidential Professor at the University of Pennsylvania School of Veterinary Medicine. He is also the Associate Director for Institute of Infectious and Zoonotic Disease (PennVet), and an affiliated Scientist at the Monell Chemical Senses Center.

References

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  6. ↑ O'Donnell, Anne Marie; Nakamura, Hiroki; Puri, Prem (2019-11-10). ""Tuft Cells": A New Player in Hirschsprung's Disease". European Journal of Pediatric Surgery. 30 (1): s–0039–1700549. doi:10.1055/s-0039-1700549. ISSN   0939-7248. PMID   31707728. S2CID   207936025.
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  10. ↑ Reid L, Meyrick B, Antony VB, Chang LY, Crapo JD, Reynolds HY (July 2005). "The mysterious pulmonary brush cell: a cell in search of a function". American Journal of Respiratory and Critical Care Medicine. 172 (1): 136–9. doi:10.1164/rccm.200502-203WS. PMC   2718446 . PMID   15817800.
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