Cutting edge: Dab2 is a FOXP3 target gene required for regulatory T cell function.
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 TGFbeta 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.
Jain
Nitya
N
Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Nguyen
Hai
H
Friedline
Randall H
RH
Malhotra
Nidhi
N
Brehm
Michael
M
Koyanagi
Madoka
M
Bix
Mark
M
Cooper
Jonathan A
JA
Chambers
Cynthia A
CA
Kang
Joonsoo
J
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000378:metabolism / Q000502:physiology*; D017629:Gap Junctions / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C478773:Dab2 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse