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FOXP3: Required but Not Sufficient. The Role of GARP (LRRC32) as a Safeguard of the Regulatory Phenotype

[ Vol. 10 , Issue. 6 ]

Author(s):

M. Probst-Kepper, R. Balling and J. Buer   Pages 533 - 539 ( 7 )

Abstract:


FOXP3 is essential for the development and function of regulatory CD4+CD25hi T (Treg) 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 predominantly (GARP, or LRRC32) is a Treg-specific receptor that binds latent TGF-β 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 Treg cells. This viewpoint focuses on GARP as safeguard of FOXP3 and the regulatory phenotype.

Keywords:

Regulatory T cells, FOXP3, GARP, TGF-β, LAP, positive feedback

Affiliation:

Institut fur Mikrobiologie, Immunologie und Krankenhaushygiene, Stadtisches Klinikum Braunschweig gGmbH1, Celler Str. 38, D-38114 Braunschweig, Germany.



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