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Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):14103-14108. Epub 2016 Nov 21.

Singular role for T-BET+CXCR3+ regulatory T cells in protection from autoimmune diabetes.

Author information

1
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
2
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 cbdm@hms.harvard.edu.

Abstract

Foxp3+ 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+ 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+ 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.

KEYWORDS:

Treg subsets; immunogenomics; immunoregulation

PMID:
27872297
PMCID:
PMC5150376
DOI:
10.1073/pnas.1616710113
[Indexed for MEDLINE]
Free PMC Article

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