Cutting edge: Dab2 is a FOXP3 target gene required for regulatory T cell function

N Jain, H Nguyen, RH Friedline, N Malhotra… - The Journal of …, 2009 - journals.aai.org
N Jain, H Nguyen, RH Friedline, N Malhotra, M Brehm, M Koyanagi, M Bix, JA Cooper
The Journal of Immunology, 2009journals.aai.org
FOXP3-expressing regulatory T (Treg) cells are vital for maintaining peripheral T cell
tolerance and homeostasis. The mechanisms by which FOXP3 target genes orchestrate
context-dependent Treg cell function are largely unknown. In this study we show that in
mouse peripheral lymphocytes the Drosophila Disabled-2 (Dab2) homolog, a gene that is
involved in enhancing TGFβ responses, is exclusively expressed in FOXP3+ regulatory T
cells. Dab2 is a direct target of FOXP3, and regulatory T cells lacking DAB2 are functionally …
Abstract
FOXP3-expressing regulatory T (Treg) cells are vital for maintaining peripheral T cell tolerance and homeostasis. The mechanisms by which FOXP3 target genes orchestrate context-dependent Treg cell function are largely unknown. In this study we show that in mouse peripheral lymphocytes the Drosophila Disabled-2 (Dab2) homolog, a gene that is involved in enhancing TGFβ responses, is exclusively expressed in FOXP3+ regulatory T cells. Dab2 is a direct target of FOXP3, and regulatory T cells lacking DAB2 are functionally impaired in vitro and in vivo. However, not all aspects of Treg cell function are perturbed, and DAB2 appears to be dispensable for Treg cell function in maintaining naive T cell homeostasis.
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