Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma.
Interferon-gamma and interleukin 12 produced by the innate arm of the immune system are important regulators of T helper type 1 (T(H)1) cell development, but signals that negatively regulate their expression remain controversial. Here we show that transforming growth factor-beta (TGF-beta) controlled T(H)1 differentiation through the regulation of interferon-gamma produced by natural killer (NK) cells. Blockade of TGF-beta signaling in NK cells caused the accumulation of a large pool of NK cells secreting copious interferon-gamma, responsible for T(H)1 differentiation and protection from leishmania infection. In contrast, blockade of TGF-beta signaling in dendritic cells did not affect dendritic cell homeostasis or interleukin 12 production, thus indicating a previously undescribed demarcation of the function of TGF-beta in NK cells versus dendritic cells.
Laouar
Yasmina
Y
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Sutterwala
Fayyaz S
FS
Gorelik
Leonid
L
Flavell
Richard A
RA
D000818:Animals; D001483:Base Sequence; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D004274:DNA, Recombinant / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D039521:CD11c Antigen; D004274:DNA, Recombinant; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II