FOXP3: required but not sufficient. the role of GARP (LRRC32) as a safeguard of the regulatory phenotype.
FOXP3 is essential for the development and function of regulatory CD4(+)CD25(hi) T (T(reg)) cells. However, recent evidence suggests that FOXP3 alone is not sufficient to completely explain the regulatory phenotype of these key players in autoimmunity and inflammation: after being activated, conventional human CD4(+) T cells transiently up-regulate FOXP3 without acquiring a regulatory function. Researchers have recently found that glycoprotein A repetitions predominant (GARP, or LRRC32) is a T(reg)-specific receptor that binds latent TGF-beta and dominantly controls FOXP3 and the regulatory phenotype via a positive feedback loop. This finding provides a missing link in our molecular understanding of FOXP3 in T(reg) cells. This viewpoint focuses on GARP as safeguard of FOXP3 and the regulatory phenotype.
Probst-Kepper
M
M
Institute for Microbiology, Immunology and Hygiene, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany. m.probst-kepper@klinikum-braunschweig.de
Balling
R
R
Buer
J
J
D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C087215:LRRC32 protein, human; D008565:Membrane Proteins; D016212:Transforming Growth Factor beta