Transit-Amplifying Cells Coordinate Changes in Intestinal Epithelial Cell-Type Composition

Sanman, Laura E.; Chen, Ina W.; Bieber, Jake M.; Steri, Veronica; Trentesaux, Chantal; Hann, Byron; Klein, Ophir D.; Wu, Lani F.; Altschuler, Steven J.

doi:10.1016/j.devcel.2020.12.020

Cited by 36 publications

(45 citation statements)

References 54 publications

(74 reference statements)

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“…2 and Supplementary Fig. 2); recent studies showed similar impact of these cytokines on intestinal epithelium 18 . Unexpectedly, these alterations were accompanied by dramatic overgrowth of follicle-associated mites with characteristics of Demodex species (Fig.…”

Section: Mainsupporting

confidence: 61%

“…Intriguingly, ILC2s in intestinal mucosa regulate homeostasis with the protozoan, Tritrichomonas 28, 29 , suggesting a role for these innate immune cells and type 2 immunity in sustaining tissue functionality in the setting of complex barrier-associated eukaryotic pathobionts. Inhibitory effects of IL-4/13 on intestinal epithelial proliferation and differentiation have been described 18 , and further work is needed to clarify these pathways. Although we cannot exclude a role for microbiota-mediated inflammation contributing to the inflammatory phenotype caused by Demodex outgrowth, the infection was controlled by topical therapeutics targeting the mite but not by antibiotics.…”

Section: Discussionmentioning

confidence: 99%

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Type 2 innate immunity regulates hair follicle homeostasis to control Demodex pathosymbionts

Kotas

Tenvooren

et al. 2021

Preprint

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Allergic skin diseases are common, but basal roles for type 2 immunity in cutaneous homeostasis are incompletely understood. Here, we show that skin group 2 innate lymphoid cells (ILC2s) are the predominant resident cells that secretes IL-13, which attenuates epithelial cell proliferation during anagen throughout the hair follicle (HF), including in HF stem cells. Although HF are normal in the absence of type 2 immunity, colonization with the commensal mite, Demodex musculi, results in epithelial proliferation and aberrant hair follicle morphology accompanied by loss of stable commensalism with massive infestation and expansion of inflammatory ILC2s and other immune cells. Topical anti-parasitic agents, but not broad-spectrum antibiotics, reversed the phenotype. Commensal Demodex colonization of mammalian hair follicles is ubiquitous, including in humans, revealing an unanticipated role for ILC2s and type 2 immunity for skin homeostasis in the normal environment.

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Section: Mainsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Type 2 innate immunity regulates hair follicle homeostasis to control Demodex pathosymbionts

Kotas

Tenvooren

et al. 2021

Preprint

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“…This is grounded in our belief that homeostasis is sometimes best understood upon perturbation of the steady-state (16) . Our ability to grow intestinal epithelial organoids in culture is also helping advance lineage reconstruction endeavors, as these constitute a readily accessible platform that facilitates batched and controlled biochemical perturbation of multiple signaling pathways simultaneously (118,119). Organoids have also been used in combination with lineage tracing and scRNA-seq-based lineage inference to aid our understanding of new putative stem/progenitor cell populations, the injury-repair process, and disease (72,120,121).…”

Section: Discussionmentioning

confidence: 99%

Cellular origins and lineage relationships of the intestinal epithelium

Capdevila

Trifas

Miller

et al. 2021

American Journal of Physiology-Gastrointestinal and Liver Physi

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Knowledge of the development and hierarchical organization of tissues is key to understanding how they are perturbed in injury and disease, as well as how they may be therapeutically manipulated to restore homeostasis. The rapidly regenerating intestinal epithelium harbors diverse cell types and their lineage relationships have been studied using numerous approaches, from classical label-retaining and genetic lineage tracing methods to novel transcriptome-based annotations. Here, we describe the developmental trajectories that dictate differentiation and lineage specification in the intestinal epithelium. We focus on the most recent single-cell RNA-sequencing (scRNA-seq)-based strategies for understanding intestinal epithelial cell lineage relationships, underscoring how they have refined our view of the development of this tissue and highlighting their advantages and limitations. We emphasize how these technologies have been applied to understand the dynamics of intestinal epithelial cells in homeostatic and injury-induced regeneration models.

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“…Finally, differentiation and maturation is needed to reestablish and maintain the mucosal barrier function. Under normal conditions, Lgr5 + intestinal stem cells (ISCs), which are located at the base of the crypts, differentiate into short-lived proliferating transit-amplifying progenitors, which further differentiate into absorptive (enterocyte) and secretory progenitors under the control of Wnt/Notch signaling [reviewed in (32,33)]. Secretory precursors then develop into enteroendocrine cells in a Neurog3-dependent manner or into Goblet or Paneth cells following activation of Atoh1 also known as Math1.…”

Section: Intestinal Epithelial Wound Healingmentioning

confidence: 99%

Intestinal Mucosal Wound Healing and Barrier Integrity in IBD–Crosstalk and Trafficking of Cellular Players

et al. 2021

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The intestinal epithelial barrier is carrying out two major functions: restricting the entry of potentially harmful substances while on the other hand allowing the selective passage of nutrients. Thus, an intact epithelial barrier is vital to preserve the integrity of the host and to prevent development of disease. Vice versa, an impaired intestinal epithelial barrier function is a hallmark in the development and perpetuation of inflammatory bowel disease (IBD). Besides a multitude of genetic, molecular and cellular alterations predisposing for or driving barrier dysintegrity in IBD, the appearance of intestinal mucosal wounds is a characteristic event of intestinal inflammation apparently inducing breakdown of the intestinal epithelial barrier. Upon injury, the intestinal mucosa undergoes a wound healing process counteracting this breakdown, which is controlled by complex mechanisms such as epithelial restitution, proliferation and differentiation, but also immune cells like macrophages, granulocytes and lymphocytes. Consequently, the repair of mucosal wounds is dependent on a series of events including coordinated trafficking of immune cells to dedicated sites and complex interactions among the cellular players and other mediators involved. Therefore, a better understanding of the crosstalk between epithelial and immune cells as well as cell trafficking during intestinal wound repair is necessary for the development of improved future therapies. In this review, we summarize current concepts on intestinal mucosal wound healing introducing the main cellular mediators and their interplay as well as their trafficking characteristics, before finally discussing the clinical relevance and translational approaches to therapeutically target this process in a clinical setting.

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Transit-Amplifying Cells Coordinate Changes in Intestinal Epithelial Cell-Type Composition

Cited by 36 publications

References 54 publications

Type 2 innate immunity regulates hair follicle homeostasis to control Demodex pathosymbionts

Type 2 innate immunity regulates hair follicle homeostasis to control Demodex pathosymbionts

Cellular origins and lineage relationships of the intestinal epithelium

Intestinal Mucosal Wound Healing and Barrier Integrity in IBD–Crosstalk and Trafficking of Cellular Players

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