In vivo reprogramming of UV radiation–induced regulatory T-cell migration to inhibit the elicitation of contact hypersensitivity

Background Regulatory T (Treg) cells induced by UV radiation (UVR) inhibit only the induction and not the elicitation of contact hypersensitivity (CHS) because they migrate into the lymph nodes but not the skin. The tissue-homing receptor expression and migratory behavior of Treg cells can be altere...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2011-10, Vol.128 (4), p.826-833
Main Authors: Schwarz, Agatha, PhD, Navid, Fatemeh, PhD, Sparwasser, Tim, MD, Clausen, Björn E., PhD, Schwarz, Thomas, MD
Format: Article
Language:English
Subjects:
Allergens - adverse effects
Allergens - pharmacology
Allergy and Immunology
Animals
Antigen-presenting cells
Antigen-Presenting Cells - immunology
Antigens, Surface - genetics
Antigens, Surface - immunology
Biological and medical sciences
Cell Movement - genetics
Cell Movement - immunology
Cell Movement - radiation effects
Cells, Cultured
Coculture Techniques
contact hypersensitivity
Dermatitis, Contact - genetics
Dermatitis, Contact - immunology
forkhead box protein 3
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Knock-In Techniques
Humans
Immunopathology
immunosuppression
in vivo reprogramming
Langerhans cells
Lectins, C-Type - genetics
Lectins, C-Type - immunology
Lymph Nodes - immunology
Mannose-Binding Lectins - genetics
Mannose-Binding Lectins - immunology
Medical sciences
Mice
Mice, Transgenic
regulatory T cells
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
skin
T-Lymphocytes, Regulatory - immunology
tissue homing
Ultraviolet Rays
UV radiation
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Summary:Background Regulatory T (Treg) cells induced by UV radiation (UVR) inhibit only the induction and not the elicitation of contact hypersensitivity (CHS) because they migrate into the lymph nodes but not the skin. The tissue-homing receptor expression and migratory behavior of Treg cells can be altered by means of in vitro coincubation with skin-derived antigen-presenting cells. On this in vitro treatment, Treg cells migrate into the skin and thus inhibit the elicitation of CHS. Objective We attempted to determine whether Treg cells can be induced by UVR in sensitized mice and manipulated entirely in vivo in such a way that they suppress the elicitation of immune responses. Methods Treg cells were induced by applying contact allergens onto UV-exposed skin in wild-type, langerin diphtheria toxin receptor knock-in, or depletion of Treg cell transgenic mice. Results UVR-induced Treg cells inhibit the elicitation of CHS in sensitized mice when stimulated by means of an antigen-specific boost through the skin. This requires cutaneous antigen-presenting cells that alter the migratory behavior of Treg cells and drive them out of the lymph nodes into the skin. Conclusions The indication is that antigen-specific Treg cells can be induced in sensitized hosts and manipulated in such a way that they suppress the elicitation of specific immune reactions. Because this is achieved entirely in vivo without invasive interventions, our findings might have important implications for strategies aiming to induce and use Treg cells in a therapeutic setting.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2011.06.005