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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
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Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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The small intestine exhibits a unique histological structure that significantly enhances its function in digestion and nutrient absorption. These structures include circular folds, villi, and various specialized cells that collectively facilitate the digestion of food.
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ILC3s mediate intestinal immune-epithelial interactions via TGF-β1 activation.

Diana Coman1, John W Bassett2, Isabelle Coales1

  • 1Centre for Host-Microbiome Interactions, King's College London, London, United Kingdom.

Mucosal Immunology
|November 29, 2025
PubMed
Summary

Innate Lymphoid Cells (ILCs) regulate gut health by producing Transforming Growth Factor-Beta 1 (TGF-β1). This study shows ILC3s use TGF-β1 to promote gut healing and immune balance, offering potential IBD treatments.

Keywords:
ILC3Innate Lymphoid CellsIntestineOrganoidsRegulatory T cellsTGF-β1

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Intravital Imaging of Intraepithelial Lymphocytes in Murine Small Intestine
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Area of Science:

  • Immunology
  • Gastroenterology
  • Cell Biology

Background:

  • Inflammatory Bowel Disease (IBD) involves gut inflammation and immune cell dysfunction.
  • Innate Lymphoid Cells (ILCs), particularly ILC3s, are crucial for maintaining intestinal homeostasis.
  • ILC3s interact with epithelial and adaptive immune cells to regulate gut health.

Purpose of the Study:

  • To investigate the role of ILC3s in modulating gastrointestinal immune responses.
  • To elucidate the mechanism by which ILC3s influence intestinal epithelial cells and T cells.
  • To explore the potential of ILC3-derived TGF-β1 as a therapeutic target in IBD.

Main Methods:

  • Analysis of murine and human ILC3 populations and their cytokine production.
  • Investigation of TGF-β1 synthesis and activation pathways in ILC3s.
  • Assessment of ILC3-mediated effects on regulatory T cells and intestinal epithelial cells.

Main Results:

  • Murine and human ILC3s synthesize and activate latent TGF-β1 via mechanical and proteolytic means.
  • ILC3-derived TGF-β1 induces FoxP3+ regulatory T cells and promotes epithelial regeneration.
  • While the downstream effects are conserved, TGF-β1 activators differ between human and mouse ILC3s.
  • ILC3s are reduced in inflamed IBD tissues, but their TGF-β1 machinery remains functional.

Conclusions:

  • ILC3s play a significant role in intestinal homeostasis through TGF-β1 secretion and activation.
  • Targeting ILC3-derived TGF-β1 may offer a novel therapeutic strategy for IBD.
  • The conserved function of TGF-β1 highlights its importance in gut health across species.