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Updated: May 5, 2026

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Homeostatic maturation programs drive human cDC2s into a tolerogenic state.

Mengmeng Lu1, Runpeng Han1, Hao Yang1

  • 1Department of Otolaryngology, Head and Neck Surgery, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, State Key Laboratory of Virology and Biosafety, Wuhan University, Wuhan 430071, China; Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.

Immunity
|February 19, 2026
PubMed
Summary

Researchers discovered a new way dendritic cells (DCs) help maintain immune tolerance in humans. A specific type of DC, called conventionally-dendritic cells type 2 (cDC2s), can promote regulatory T cells (Tregs) to prevent immune overreactions.

Keywords:
dendritic cellshomeostatic maturationimmune toleranceregulatory T cellsthymic stromal lymphopoietintissue- restricted self-antigens

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Area of Science:

  • Immunology
  • Cell Biology
  • Human Physiology

Background:

  • Dendritic cells (DCs) are key regulators of immune responses, balancing activation and tolerance.
  • While DC roles in immunity are known, human peripheral tolerance mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the mechanisms of human peripheral tolerance mediated by dendritic cells.
  • To identify novel DC maturation programs and their role in immune regulation.

Main Methods:

  • Multi-omics analysis of human splenic dendritic cell maturation.
  • Identification and characterization of a specific DC subset (cDC2s) and their maturation program.
  • Functional assays assessing T cell conversion and cytokine stimulation effects.

Main Results:

  • A homeostatic maturation program was identified in type 2 conventional dendritic cells (cDC2s).
  • These homeostatically matured cDC2s (DC2hm) upregulate tolerance-associated transcripts, Treg-polarizing machinery, and the TSLP receptor complex.
  • IL-7Rα+CCR7+ DC2hm cells effectively convert naive CD4+ T cells into FOXP3+ Treg cells.
  • Thymic stromal lymphopoietin (TSLP) stimulation induces the DC2hm phenotype, highlighting its role in tolerance.

Conclusions:

  • A novel human cDC2 homeostatic maturation program (DC2hm) has been delineated.
  • DC2hm cells are identified as potential mediators of human peripheral tolerance.
  • Findings offer insights into autoimmune disease and the development of tolerance-inducing therapies.