Dexamethasone upregulates FOXP3 expression without increasing regulatory activity.
Recent studies have shown the capacity of corticoids to increase forkhead box p3 (FOXP3) expression, which suggests that these drugs may be able to generate regulatory T cells (Treg). Therefore, corticoids may possibly be employed in protocols to generate or expand Treg cells with the aim of being used in cell transfer therapy. However, given that in humans FOXP3 is not necessarily associated with regulatory function, it is of great importance to ascertain whether FOXP3-expressing cells generated with corticoids are "truly" Treg cells. To this end, we studied the effect of dexamethasone on both human activated lymphocytes and in vitro generated Treg cells as well as regulatory activity of CD4(+)CD25(high) cells from SLE patients users and non users of prednisone. Results show that dexamethasone markedly enhances FOXP3 expression and generates CD25(high) cells with phenotypic characteristics attributable to natural Treg cells. Unexpectedly, in spite of their hyporesponsiveness and enhanced FOXP3 expression, these cells did not exert suppressive activity. Moreover, although dexamethasone was able to enhance FOXP3 expression in in vitro generated Treg cells, once again this effect was not correlated with increased regulatory activity. These results were supported by the fact that CD4(+)CD25(high) cells from steroid-treated SLE patients did not show a higher antiproliferative function than those from non-steroid-treated patients. We conclude that the increment on FOXP3 expression caused by dexamethasone is not connected with regulatory function, supporting the fact that FOXP3 expression in humans is not an exclusive attribute of Treg cells. Subsequently, the use of FOXP3 as a Treg cell marker must be done cautiously, especially in patients with systemic inflammatory diseases or those under corticoid treatment.
Prado
Catuxa
C
Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, C/Julián Clavería s/n, 33006 Oviedo, Spain.
Gómez
Jesús
J
López
Patricia
P
de Paz
Banesa
B
Gutiérrez
Carmen
C
Suárez
Ana
A
D000328:Adult; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D003907:Dexamethasone; D011241:Prednisone