G protein-coupled receptor 83 overexpression in naive CD4+CD25- T cells leads to the induction of Foxp3+ regulatory T cells in vivo.
Foxp3 functions as a lineage specification factor for the development of naturally occurring thymus-derived CD4+CD25+ regulatory T (Treg) cells. Recent evidence suggests that naive Foxp3-CD4+CD25- T cells can be converted in the periphery into Foxp3+ Treg cells. In this study, we have identified the G protein-coupled receptor (GPR)83 to be selectively up-regulated by CD4+CD25+ Treg cells of both murine and human origin in contrast to naive CD4+CD25- or recently activated T cells. Furthermore, GPR83 was induced upon overexpression of Foxp3 in naive CD4+CD25- T cells. Transduction of naive CD4+CD25- T cells with GPR83-encoding retroviruses did not confer in vitro suppressive activity. Nevertheless, GPR83-transduced T cells were able to inhibit the effector phase of a severe contact hypersensitivity reaction of the skin, indicating that GPR83 itself or GPR83-mediated signals conferred suppressive activity to conventional CD4+ T cells in vivo. Most strikingly, this in vivo acquisition of suppressive activity was associated with the induction of Foxp3 expression in GPR83-transduced CD4+ T cells under inflammatory conditions. Our results suggest that GPR83 might be critically involved in the peripheral generation of Foxp3+ Treg cells in vivo.
Hansen
Wiebke
W
Department of Mucosal Immunity, German Research Centre for Biotechnology, Mascheroder Weg 1, 38124 Braunschweig, Germany.
Loser
Karin
K
Westendorf
Astrid M
AM
Bruder
Dunja
D
Pfoertner
Susanne
S
Siewert
Christiane
C
Huehn
Jochen
J
Beissert
Stefan
S
Buer
Jan
J
D019264:Adoptive Transfer; D000818:Animals; D018920:Coculture Techniques; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000821:virology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C501983:GPR83 protein, human; C501984:Gpr83 protein, mouse; D043562:Receptors, G-Protein-Coupled; D015375:Receptors, Interleukin-2