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Singular role for T-BET+CXCR3+ regulatory T cells in protection from autoimmune diabetes.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2016 Dec 06; Vol. 113 (49), pp. 14103-14108. Date of Electronic Publication: 2016 Nov 21. - Publication Year :
- 2016
-
Abstract
- Foxp3 <superscript>+</superscript> regulatory T (Treg) cells are crucial for restraining inflammation in a variety of autoimmune diseases, including type 1 diabetes (T1D). However, the transcriptional and functional phenotypes of Treg cells within the pancreatic lesion remain poorly understood. Here we characterized pancreas-infiltrating Treg cells in the NOD mouse model of T1D and uncovered a substantial enrichment of the Treg subpopulation expressing the chemokine receptor CXCR3. Accumulation of CXCR3 <superscript>+</superscript> Treg cells within pancreatic islets was dependent on the transcription factor T-BET, and genetic ablation of T-BET increased the onset and penetrance of disease, abrogating the sex bias normally seen in the NOD model. Both male and female mice lacking T-BET <superscript>+</superscript> Treg cells showed a more aggressive insulitic infiltrate, reflected most prominently by elevated production of type 1 cytokines. Our results suggest the possibility of fine therapeutic targeting of Treg cells, in a tissue- and cell-subset-specific fashion, as a more focused immunotherapy for T1D.<br />Competing Interests: The authors declare no conflict of interest.
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 113
- Issue :
- 49
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 27872297
- Full Text :
- https://doi.org/10.1073/pnas.1616710113