Murine plasmacytoid dendritic cells produce IFN-gamma upon IL-4 stimulation.
IL-4 plays a key role in inducing IL-4 production in CD4+ T cells, functioning as an important determinant for Th2 cell differentiation. We show here that IL-4 induces IFN-gamma production in B220+ plasmacytoid dendritic cells (PDCs). By searching for cell populations that produce IFN-gamma upon IL-4 stimulation, we found that PDCs were a major IFN-gamma-producing cell upon IL-4 stimulation in wild-type and Rag-2-/- splenocytes. Isolated PDCs, but not CD11b+ DCs or CD8+ DCs, produced IFN-gamma upon IL-4 stimulation. In vivo, the depletion of PDCs by anti-Ly6G/C Ab prevented IFN-gamma production induced by IL-4 administration. We also found that IL-4 induced IFN-gamma production, but not IL-12 or IFN-alpha production, in PDCs and also strongly enhanced CpG oligodeoxynucleotide-induced IFN-gamma production, but not CpG oligodeoxynucleotide-induced IL-12 or IFN-alpha production. However, IL-4 did not induce IFN-gamma production in Stat6-/- PDCs. Moreover, IL-4 induced Stat4 expression in PDCs through a Stat6-dependent mechanism, and only the Stat4-expressing PDCs produced IFN-gamma. Furthermore, IL-4 did not induce IFN-gamma production in Stat4-/- PDCs. These results indicate that PDCs preferentially produce IFN-gamma upon IL-4 stimulation by Stat6- and Stat4-dependent mechanisms.
Suto
Akira
A
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Nakajima
Hiroshi
H
Tokumasa
Naoki
N
Takatori
Hiroaki
H
Kagami
Shin-ichiro
S
Suzuki
Kotaro
K
Iwamoto
Itsuo
I
D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D007370:Interferon Type I / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000502:physiology; D015847:Interleukin-4 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D010950:Plasma Cells / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D050797:STAT4 Transcription Factor / Q000235:genetics; D050800:STAT6 Transcription Factor / Q000502:physiology; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000235:genetics; D000098815:T-bet Transcription Factor
D039481:CD11b Antigen; D007370:Interferon Type I; D012333:RNA, Messenger; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens