Abstract
Dendritic cells (DCs) are highly susceptible to extrinsic signals that modify the functions of these crucial APCs. Maturation of DCs induced by diverse proinflammatory conditions promotes immune responses, but certain signals also induce tolerogenic functions in DCs. These “induced tolerogenic DCs” help to moderate immune responses such as those to commensals present at specific anatomical locations. However, also under steady-state conditions, some DCs are characterized by inherent tolerogenic properties. The immunomodulatory mechanisms constitutively present in such “natural tolerogenic DCs” help to promote tolerance to peripheral Ags. By extending tolerance initially established in the thymus, these functions of DCs help to regulate autoimmune and other immune responses. In this review we will discuss the mechanisms and functions of natural and induced tolerogenic DCs and offer further insight into how their possible manipulations may ultimately lead to more precise treatments for various immune-mediated conditions and diseases.
Footnotes
This work was supported in part by National Institute of Allergy and Infectious Diseases/National Institutes of Health Grant R01AI113903 (to D.H.).
Abbreviations used in this article:
- AHR
- aryl hydrocarbon receptor
- BMDC
- bone marrow–derived DC
- BTLA
- B and T lymphocyte associated
- cDC
- conventional DC
- DC
- dendritic cell
- DC-SIGN
- DC-specific ICAM-3–grabbing nonintegrin
- EAE
- experimental autoimmune encephalomyelitis
- HVEM
- herpesvirus entry mediator
- itDC
- induced tolerogenic DC
- LN
- lymph node
- MHCII
- MHC class II
- moDC
- monocyte-derived DC
- MS
- multiple sclerosis
- mTOR
- mammalian target of rapamycin
- ntDC
- natural tolerogenic DC
- PD-1
- programmed death-1
- pDC
- plasmacytoid DC
- PD-L1
- programmed death ligand-1
- PRR
- pattern recognition receptor
- pTreg
- peripherally formed Treg
- RA
- retinoic acid
- Treg
- regulatory T
- tTreg
- thymically derived regulatory T
- VDR
- vitamin D receptor.
- Received September 16, 2019.
- Accepted October 4, 2019.
- Copyright © 2020 by The American Association of Immunologists, Inc.
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