IFN-γ and IL-12 synergize to convert in vivo generated Th17 into Th1/Th17 cells.
Th1 and Th17 cells are distinct lineages of effector/memory cells, imprinted for re-expression of IFN-γ and IL-17, by upregulated expression of T-bet and retinoic acid-related orphan receptor γt (RORγt), respectively. Apparently, Th1 and Th17 cells share tasks in the control of inflammatory immune responses. Th cells coexpressing IFN-γ and IL-17 have been observed in vivo, but it remained elusive, how these cells had been generated and whether they represent a distinct lineage of Th differentiation. It has been shown that ex vivo isolated Th1 and Th17 cells are not interconvertable by TGF-β/IL-6 and IL-12, respectively. Here, we show that ex vivo isolated Th17 cells can be converted into Th1/Th17 cells by combined IFN-γ and IL-12 signaling. IFN-γ is required to upregulate expression of the IL-12Rβ2 chain, and IL-12 for Th1 polarization. These Th1/Th17 cells stably coexpress RORγt and T-bet at the single-cell level. Our results suggest a molecular pathway for the generation of Th1/Th17 cells in vivo, which combine the pro-inflammatory potential of Th1 and Th17 cells.
Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute, Berlin, Germany.
Maria H
MH
Lexberg
Annegret
A
Taubner
Inka
I
Albrecht
Inga
I
Lepenies
Anne
A
Richter
Thomas
T
Kamradt
Andreas
A
Radbruch
Hyun-Dong
HD
Chang
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000819:agonists / Q000276:immunology*; D018664:Interleukin-12 / Q000819:agonists / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology; D053707:Receptors, Interleukin-12 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D000098815:T-bet Transcription Factor
C508439:IL12RB2 protein, human; C508600:IL6 protein, human; C508443:Il12rb2 protein, mouse; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D053707:Receptors, Interleukin-12; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D007371:Interferon-gamma