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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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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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TGF - β Signaling Pathway01:16

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Renewal of Intestinal Stem Cells01:23

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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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In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
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A RORγt+ cell instructs gut microbiota-specific Treg cell differentiation.

Ranit Kedmi1, Tariq A Najar1, Kailin R Mesa1

  • 1Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY, USA.

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Gut bacteria guide immune responses by signaling through specific antigen-presenting cells. RORγt+ cells, not dendritic cells, are crucial for inducing regulatory T cells (Treg) to maintain gut homeostasis.

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Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • The gut microbiota and host immune system maintain a symbiotic relationship crucial for homeostasis.
  • Imbalances in this relationship can lead to inflammatory conditions like Crohn's disease.
  • Gut bacteria, such as Helicobacter species, influence adaptive immune responses, directing T cell differentiation.

Purpose of the Study:

  • To investigate the specific cells and molecular mechanisms involved in induced regulatory T cell (iTreg) differentiation.
  • To understand how gut bacteria direct T cells towards distinct functional fates.

Main Methods:

  • Investigated antigen presentation pathways required for iTreg cell induction.
  • Analyzed the role of RORγt-expressing cells in T cell differentiation.
  • Examined the necessity of the antigen-presentation machinery, CCR7, and αv integrin for iTreg induction.

Main Results:

  • Antigen presentation by RORγt+ cells (likely innate lymphoid cells) is required and sufficient for iTreg induction, not classical dendritic cells.
  • RORγt+ cells require specific molecular components (antigen-presentation machinery, CCR7, αv integrin) for iTreg differentiation.
  • Absence of these factors leads to the expansion of pathogenic T helper 17 (TH17) cells.

Conclusions:

  • Intestinal microbes utilize distinct antigen-presenting cells with pre-programmed features to direct specific T cell differentiation.
  • This targeted approach ensures appropriate immune responses, distinguishing between regulatory and inflammatory pathways.