Layers of dendritic cell-mediated T cell tolerance, their regulation and the prevention of autoimmunity.

2.50
Hdl Handle:
http://hdl.handle.net/10033/322783
Title:
Layers of dendritic cell-mediated T cell tolerance, their regulation and the prevention of autoimmunity.
Authors:
Mayer, Christian T; Berod, Luciana; Sparwasser, Tim ( 0000-0001-5645-902X )
Abstract:
The last decades of Nobel prize-honored research have unequivocally proven a key role of dendritic cells (DCs) at controlling both T cell immunity and tolerance. A tight balance between these opposing DC functions ensures immune homeostasis and host integrity. Its perturbation could explain pathological conditions such as the attack of self tissues, chronic infections, and tumor immune evasion. While recent insights into the complex DC network help to understand the contribution of individual DC subsets to immunity, the tolerogenic functions of DCs only begin to emerge. As these consist of many different layers, the definition of a "tolerogenic DC" is subjected to variation. Moreover, the implication of DCs and DC subsets in the suppression of autoimmunity are incompletely resolved. In this review, we point out conceptual controversies and dissect the various layers of DC-mediated T cell tolerance. These layers include central tolerance, Foxp3(+) regulatory T cells (Tregs), anergy/deletion and negative feedback regulation. The mode and kinetics of antigen presentation is highlighted as an additional factor shaping tolerance. Special emphasis is given to the interaction between layers of tolerance as well as their differential regulation during inflammation. Furthermore, potential technical caveats of DC depletion models are considered. Finally, we summarize our current understanding of DC-mediated tolerance and its role for the suppression of autoimmunity. Understanding the mechanisms of DC-mediated tolerance and their complex interplay is fundamental for the development of selective therapeutic strategies, e.g., for the modulation of autoimmune responses or for the immunotherapy of cancer.
Affiliation:
Institute of Infection Immunology, TWINCORE/Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Straβe7, 30625 Hannover, Germany.
Citation:
Layers of dendritic cell-mediated T cell tolerance, their regulation and the prevention of autoimmunity. 2012, 3:183 Front Immunol
Journal:
Frontiers in immunology
Issue Date:
2012
URI:
http://hdl.handle.net/10033/322783
DOI:
10.3389/fimmu.2012.00183
PubMed ID:
22783257
Type:
Article
Language:
en
ISSN:
1664-3224
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorMayer, Christian Ten
dc.contributor.authorBerod, Lucianaen
dc.contributor.authorSparwasser, Timen
dc.date.accessioned2014-07-10T13:08:09Zen
dc.date.available2014-07-10T13:08:09Zen
dc.date.issued2012en
dc.identifier.citationLayers of dendritic cell-mediated T cell tolerance, their regulation and the prevention of autoimmunity. 2012, 3:183 Front Immunolen
dc.identifier.issn1664-3224en
dc.identifier.pmid22783257en
dc.identifier.doi10.3389/fimmu.2012.00183en
dc.identifier.urihttp://hdl.handle.net/10033/322783en
dc.description.abstractThe last decades of Nobel prize-honored research have unequivocally proven a key role of dendritic cells (DCs) at controlling both T cell immunity and tolerance. A tight balance between these opposing DC functions ensures immune homeostasis and host integrity. Its perturbation could explain pathological conditions such as the attack of self tissues, chronic infections, and tumor immune evasion. While recent insights into the complex DC network help to understand the contribution of individual DC subsets to immunity, the tolerogenic functions of DCs only begin to emerge. As these consist of many different layers, the definition of a "tolerogenic DC" is subjected to variation. Moreover, the implication of DCs and DC subsets in the suppression of autoimmunity are incompletely resolved. In this review, we point out conceptual controversies and dissect the various layers of DC-mediated T cell tolerance. These layers include central tolerance, Foxp3(+) regulatory T cells (Tregs), anergy/deletion and negative feedback regulation. The mode and kinetics of antigen presentation is highlighted as an additional factor shaping tolerance. Special emphasis is given to the interaction between layers of tolerance as well as their differential regulation during inflammation. Furthermore, potential technical caveats of DC depletion models are considered. Finally, we summarize our current understanding of DC-mediated tolerance and its role for the suppression of autoimmunity. Understanding the mechanisms of DC-mediated tolerance and their complex interplay is fundamental for the development of selective therapeutic strategies, e.g., for the modulation of autoimmune responses or for the immunotherapy of cancer.en
dc.language.isoenen
dc.rightsArchived with thanks to Frontiers in immunologyen
dc.titleLayers of dendritic cell-mediated T cell tolerance, their regulation and the prevention of autoimmunity.en
dc.typeArticleen
dc.contributor.departmentInstitute of Infection Immunology, TWINCORE/Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Straβe7, 30625 Hannover, Germany.en
dc.identifier.journalFrontiers in immunologyen
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