GARP: a surface molecule of regulatory T cells that is involved in the regulatory function and TGF-β releasing

Abstract

There are many molecules that define regulatory T cells (Tregs) phenotypically and functionally. Glycoprotein A repetitions predominant (GARP) is a transmembrane protein containing leucine rich repeats. Recently, GARP is found to express highly on the surface of activated Tregs. The combination of GARP and other surface molecules isolates Tregs with higher purity. Besides, GARP is a cell surface molecule of Tregs that maintains their regulatory function and homeosatsis. GARP has also been proved to promote the activation and secretion of transforming growth factor β (TGF-β). Moreover, its potential value in cancer immunotherapy is also discussed in this work.

Keywords: glycoprotein A repetitions predominant; regulatory T cells; transforming growth factor β.

Figure 1. TGF-β and GARP maintain homeostasis and function of Tregs

TGF-β is synthesized as a pro-TGF-β precursor, a homodimer that includes LAP and mature TGF-β. Then pro-TGF-β are cleaved by the enzyme furin to form latent TGF-β, where mature TGF-β remain noncovalently bind to the LAP. Membrane form of GARP transports and anchors latent TGF-β to the surface of Tregs. The release of mature TGF-β from the surface latent TGF-β/GARP complex can be mediated by integrin. Mature TGF-β in turn acts on Tregs themselves, forming a positive and autocrine TGF-β feedback loop. Mature TGF-β also acts on target cells in paracrine manner. Besides, the surface latent TGF-β/GARP complex can also directly act on target cells and increases Tregs suppressive function, but the mechanism is still unclear.