Critical role of heme oxygenase-1 in Foxp3-mediated immune suppression.
Foxp3, which encodes the transcription factor scurfin, is indispensable for the development and function of CD4(+)CD25(+) regulatory T cells (Treg). Recent data suggest conversion of peripheral CD4(+)CD25(-) nai ve T cells to CD4(+)CD25(+) Treg by acquisition of Foxp3 through costimulation with TCR and TGF-beta or forced expression of the gene. One critical question is how Foxp3 causes T cells to become regulatory. In the present work, we demonstrate that Foxp3 can induce heme oxygenase-1 (HO-1) expression and subsequently such regulatory phenotypes as the suppression of nontransfected cells in a cell-cell contact-dependent manner as well as impaired proliferation and production of cytokines upon stimulation in Jurkat T cells. Moreover, we confirm the expression of both Foxp3 and HO-1 in peripheral CD4(+)CD25(+) Treg and suppressive function of the cells are relieved by the inhibition of HO-1 activity. In summary, we demonstrate that Foxp3 induces HO-1 expression and HO-1 engages in Foxp3-mediated immune suppression.
Choi
Byung-Min
BM
Department of Microbiology and Immunology, School of Medicine, and Genomic Research Center for Immune Disorders, Wonkwang University, Iksan, Chonbuk, Republic of Korea.
Pae
Hyun-Ock
HO
Jeong
Young-Ran
YR
Kim
Young-Myeong
YM
Chung
Hun-Taeg
HT
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D015973:Gene Expression Regulation, Leukemic; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D019169:Jurkat Cells; D008565:Membrane Proteins; D015375:Receptors, Interleukin-2 / Q000276:immunology; D014162:Transfection
D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D015375:Receptors, Interleukin-2; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1