IFN-lambda1 (IL-29) inhibits GATA3 expression and suppresses Th2 responses in human naive and memory T cells.
IFN-lambda1 (IL-29) plays a novel, emerging role in the inhibition of human Th2 responses. Here, we demonstrate that both naive and memory human CD4(+) T cells express mRNA for the IFN-lambda1-specific receptor, IL-28Ralpha, and are responsive to IFN-lambda1. Expression of Th2 cytokines (IL-4 and IL-13) was suppressed in naive and memory CD4(+) T cells by IFN-lambda1, without affecting their proliferation. Further, acquisition of IL-4Ralpha expression after stimulation was inhibited by IFN-lambda1, as was GATA3 expression. Finally, IFN-lambda1 diminished the change in cell-surface phenotype that accompanies differentiation of "central memory" T cells into "effector memory" T cells. Taken together, our data describe unique immunomodulatory effects of IFN-lambda1 and identify novel mechanisms for the reduction of existing Th2 responses and the regulation of new ones, in circulating naive and memory CD4(+) T cells.
Dai
Jihong
J
Genetic Immunology Laboratory, HUMIGEN, The Institute for Genetic Immunology, Hamilton, NJ 08690, USA.
Megjugorac
Nicholas J
NJ
Gallagher
Grant E
GE
Yu
Raymond Y L
RY
Gallagher
Grant
G
D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis / Q000494:pharmacology*; D018121:Receptors, Cytokine / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D007378:Interleukins; D018121:Receptors, Cytokine; C471046:interleukin 28alpha receptor