GATA3 and a dominant regulatory gene expression profile discriminate operational tolerance in human transplantation.
Some organ-transplanted patients achieve a state of "operational tolerance" (OT) in which graft function is maintained after the complete withdrawal of immunosuppressive drugs. We used a gene panel of regulatory/inflammatory molecules (FOXP3, GATA3, IL10, TGFB1, TGFBR1/ TBX21, TNF and IFNG) to investigate the gene expression profile in peripheral blood mononuclear cells of renal-transplanted individuals experiencing OT compared to transplanted individuals not displaying OT and healthy individuals (HI). OT subjects showed a predominant regulatory (REG) profile with higher gene expression of GATA3, FOXP3, TGFB1 and TGFB receptor 1 compared to the other groups. This predominant REG gene expression profile displayed stability over time. The significant GATA3 gene and protein expressions in OT individuals suggest that a Th2 deviation may be a relevant pathway to OT. Moreover, the capacity of the REG/INFLAMMA gene panel to discriminate OT by peripheral blood analysis indicates that this state has systemic repercussions.
Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil.
Pedro Manoel M
PM
Moraes-Vieira
Maisa C S
MC
Takenaka
Hernandez M
HM
Silva
Sandra Maria
SM
Monteiro
Fabiana
F
Agena
Francine
F
Lemos
David
D
Saitovitch
Jorge
J
Kalil
Verônica
V
Coelho
D000328:Adult; D000368:Aged; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000378:metabolism*; D016030:Kidney Transplantation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018125:Receptors, Transforming Growth Factor beta / Q000097:blood / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D018418:Th2 Cells / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D007166:Immunosuppressive Agents; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1