The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues

Semin Immunopathol. 2017 Feb;39(2):137-152. doi: 10.1007/s00281-016-0602-0. Epub 2016 Nov 25.

Abstract

Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu, multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells. DCs directing tolerance secrete anti-inflammatory cytokines and induce naïve T cells or B cells to differentiate into regulatory T cells (Tregs) or B cells. In this review, we provide a detailed outlook on the molecular mechanisms that induce functional specialization to govern central or peripheral tolerance. The tolerance-inducing nature of DCs can be exploited to overcome autoimmunity and rejection in graft transplantation.

Keywords: Tolerogenic DCs; cytokines; growth factors; immune homeostasis; regulatory T cells; transcription factors.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • B-Lymphocytes, Regulatory / immunology
  • B-Lymphocytes, Regulatory / metabolism
  • Cell Differentiation
  • Cross-Priming / immunology
  • Cytokines / metabolism
  • Dendritic Cells / classification
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Gene Expression Regulation
  • Hematopoietic Cell Growth Factors / metabolism
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Homeostasis
  • Humans
  • Immune Tolerance*
  • Immunomodulation
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / metabolism
  • Organ Specificity / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Vaccines / immunology

Substances

  • Cytokines
  • Hematopoietic Cell Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Transcription Factors
  • Vaccines
  • flt3 ligand protein