Cutting edge: Type I IFN reverses human Th2 commitment and stability by suppressing GATA3.
T helper 2 cells regulate inflammatory responses to helminth infections while also mediating pathological processes of asthma and allergy. IL-4 promotes Th2 development by inducing the expression of the GATA3 transcription factor, and the Th2 phenotype is stabilized by a GATA3-dependent autoregulatory loop. In this study, we found that type I IFN (IFN-alpha/beta) blocked human Th2 development and inhibited cytokine secretion from committed Th2 cells. This negative regulatory pathway was operative in human but not mouse CD4(+) T cells and was selective to type I IFN, as neither IFN-gamma nor IL-12 mediated such inhibition. IFN-alpha/beta blocked Th2 cytokine secretion through the inhibition of GATA3 during Th2 development and in fully committed Th2 cells. Ectopic expression of GATA3 via retrovirus did not overcome IFN-alpha/beta-mediated inhibition of Th2 commitment. Thus, we demonstrate a novel role for IFN-alpha/beta in blocking Th2 cells, suggesting its potential as a promising therapy for atopy and asthma.
Huber
Jonathan P
JP
Department of Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9093, USA.
Ramos
Hilario J
HJ
Gill
Michelle A
MA
Farrar
J David
JD
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D050990:GATA3 Transcription Factor; D016898:Interferon-alpha; D015847:Interleukin-4; D016899:Interferon-beta