NDLI: Foxp3 expression is required for the induction of therapeutic tissue tolerance.

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Foxp3 expression is required for the induction of therapeutic tissue tolerance.

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Foxp3 expression is required for the induction of therapeutic tissue tolerance.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Regateiro, Frederico S. Howie, Duncan Kendal, Adrian R. Adams, Elizabeth Zhang, Mindy Nolan, Kathleen F. Betz, Alexander G. Hilbrands, Robert Madhiwalla, Shruti Roberts, Bruce Chen, Ye Cobbold, Stephen P. Waldmann, Herman Ma, Jianbo Andersen, Kristian G.
Description	Country affiliation: United kingdom Author Affiliation: Regateiro FS ( Sir William Dunn School of Pathology, Oxford University, Oxford OX1 3RE, United Kingdom.)
Abstract	CD4(+)Foxp3(+) regulatory T cells (Treg) are essential for immune homeostasis and maintenance of self-tolerance. They are produced in the thymus and also generated de novo in the periphery in a TGF-ß-dependent manner. Foxp3(+) Treg are also required to achieve tolerance to transplanted tissues when induced by coreceptor or costimulation blockade. Using TCR-transgenic mice to avoid issues of autoimmune pathology, we show that Foxp3 expression is both necessary and sufficient for tissue tolerance by coreceptor blockade. Moreover, the known need in tolerance induction for TGF-ß signaling to T cells can wholly be explained by its role in induction of Foxp3, as such signaling proved dispensable for the suppressive process. We analyzed the relative contribution of TGF-ß and Foxp3 to the transcriptome of TGF-ß-induced Treg and showed that TGF-ß elicited a large set of downregulated signature genes. The number of genes uniquely modulated due to the influence of Foxp3 alone was surprisingly limited. Retroviral-mediated conditional nuclear expression of Foxp3 proved sufficient to confer transplant-suppressive potency on CD4(+) T cells and was lost once nuclear Foxp3 expression was extinguished. These data support a dual role for TGF-ß and Foxp3 in induced tolerance, in which TGF-ß stimulates Foxp3 expression, for which sustained expression is then associated with acquisition of tolerance.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1200449
Journal	The Journal of Immunology
Issue Number	8
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-10-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Forkhead Transcription Factors Biosynthesis Genetics T-lymphocytes, Regulatory Immunology Transplantation Tolerance Animals Cell Line, Tumor Deficiency Graft Survival Mice Mice, Inbred C57bl Mice, Inbred Cba Mice, Knockout Mice, Transgenic Signal Transduction T-lymphocyte Subsets Metabolism Transforming Growth Factor Beta Physiology Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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