Regulatory T (Treg) cells are the primary mediators of peripheral tolerance and their alteration is one of the major causes of autoimmune disorders. Bcl11b is an essential transcriptional regulator for T lineage differentiation and maintenance of T cell identity, as well as for innate lymphoid identity and function. Here we provide evidence that early and efficient removal of Bcl11b in Treg cells causes early death of mice despite the fact that Treg cells are formed in normal numbers. However, Bcl11b-/- Treg cells are unable to block Tcell induced colitis due to major reduction in genes controlling the conversion of extracellular ATP, released in inflammatory conditions, into suppressive pericellular adenosine, as well as IL10. We propose experiments to investigate the regulation by Bcl11b of Treg cell genetic program at steady state and in inflammatory conditions, including exploring genomic regions regulated by Bcl11b, with main emphasis on suppression function. These studies have high relevance for autoimmune diseases.

Public Health Relevance

T regulatory (Treg) cells are the primary mediators of peripheral tolerance and their alteration is one of the major causes of autoimmune disorders. This grant application aims to decipher mechanisms implicated in function of these cells, which is critical for development of therapeutic strategies for autoimmune disease treatement.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI131205-01A1
Application #
9403716
Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Ramachandra, Lakshmi
Project Start
2017-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Florida
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611