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Regulatory T-cell (Treg) selection in the thymus is essential to prevent autoimmune diseases. Although important rules for Treg selection have been established, there is controversy regarding the degree of self-reactivity displayed by T-cell receptors expressed by Treg cells. In this study we have developed a model of autoimmune skin inflammation, to determine key parameters in the generation of skin-reactive Treg cells in the thymus (tTreg). tTreg development is predominantly AIRE dependent, with an AIRE-independent component. Without the knowledge of antigen recognized by skin-reactive Treg cells, we are able to enhance skin-specific tTreg cell generation using three approaches. First, we increase medullary thymic epithelial cells by using mice lacking osteoprotegerin or by adding TRANCE (RANKL, Tnfsf11). Second, we inject intrathymically peripheral dendritic cells from skin-draining sites. Finally, we inject skin tissue lysates intrathymically. These findings have implications for enhancing the generation of organ-specific Treg cells in autoimmune diseases.

Original publication

DOI

10.1038/ncomms10562

Type

Journal article

Journal

Nature communications

Publication Date

29/02/2016

Volume

7

Addresses

The Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, New York 10016, USA.

Keywords

Epidermis, Thymus Gland, Dendritic Cells, Dermis, Animals, Chimera, Mice, Transgenic, Mice, Knockout, Mice, Dermatitis, Autoimmune Diseases, Disease Models, Animal, Receptors, Antigen, T-Cell, Transcription Factors, Flow Cytometry, Organ Culture Techniques, Autoimmunity, Self Tolerance, Antigen Presentation, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, RANK Ligand, Osteoprotegerin