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Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
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Epithelial colonization by gut dendritic cells promotes their functional diversification.

Claudia A Rivera1, Violaine Randrian1, Wilfrid Richer1

  • 1Institut Curie, INSERM U932, PSL Research University, 75005 Paris, France.

Immunity
|December 15, 2021
PubMed
Summary

Food-derived retinoic acid shapes dendritic cells (DCs) in the small intestine. This leads to distinct mature and immature DC subsets within the same tissue, influencing immune responses.

Keywords:
T cell activation and toleranceantigen presentationepitheliumimmature and mature dendritic cellsnichesmall intestinetransmigration

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Area of Science:

  • Immunology
  • Cell Biology
  • Gastroenterology

Background:

  • Dendritic cells (DCs) are crucial for initiating adaptive immunity by presenting antigens.
  • DCs exist as diverse subsets with varying functions and activation states within tissues.
  • The mechanisms orchestrating DC diversification based on tissue-specific cues are not fully understood.

Purpose of the Study:

  • To investigate how tissue-specific cues in the small intestine diversify dendritic cell (DC) populations.
  • To identify the factors responsible for the distinct phenotypes of DCs in different small intestinal niches.
  • To elucidate the role of food-derived retinoic acid in DC functional diversification.

Main Methods:

  • Analysis of dendritic cell (DC) subsets in the small intestine.
  • Investigating the impact of retinoic acid (ATRA) on DC phenotype and function.
  • Examining the role of mucus components like Muc2 in DC imprinting.

Main Results:

  • Two distinct pools of CD103+CD11b+ cDC2s were identified in the small intestine: mature-like proinflammatory cells in the lamina propria (LP) and immature-like tolerogenic cells within the epithelium.
  • Food-derived retinoic acid (ATRA) promoted the transmigration of LP cDC2s into the epithelium by enhancing actomyosin contractility.
  • DCs in distinct subtissular niches were imprinted by environmental cues, including ATRA and Muc2, leading to functional diversification.

Conclusions:

  • Dendritic cell (DC) populations in the small intestine are diversified by subtissular niche imprinting.
  • Retinoic acid (ATRA) plays a key role in differentiating DC subsets by influencing their location and phenotype.
  • DCs can exhibit both immature and mature states within the same tissue, revealing a novel mechanism for immune regulation.