Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma

Yasmina Laouar; Fayyaz S Sutterwala; Leonid Gorelik; Richard A Flavell

doi:10.1038/ni1197

Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma

Nat Immunol. 2005 Jun;6(6):600-7. doi: 10.1038/ni1197. Epub 2005 Apr 24.

Authors

Yasmina Laouar¹, Fayyaz S Sutterwala, Leonid Gorelik, Richard A Flavell

Affiliation

¹ Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

PMID: 15852008
DOI: 10.1038/ni1197

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
CD11c Antigen / genetics
CD11c Antigen / metabolism
Cell Differentiation
DNA, Recombinant / genetics
Dendritic Cells / immunology
Humans
Immunity, Innate
In Vitro Techniques
Interferon-gamma / biosynthesis*
Killer Cells, Natural / immunology*
Leishmania major / immunology
Leishmania major / pathogenicity
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Protein Serine-Threonine Kinases
Receptor, Transforming Growth Factor-beta Type II
Receptors, Transforming Growth Factor beta / genetics
Receptors, Transforming Growth Factor beta / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Recombinant Proteins / pharmacology
Signal Transduction
Th1 Cells / cytology*
Th1 Cells / immunology*
Transforming Growth Factor beta / metabolism*
Transforming Growth Factor beta / pharmacology

Substances

CD11c Antigen
DNA, Recombinant
Receptors, Transforming Growth Factor beta
Recombinant Proteins
Transforming Growth Factor beta
Interferon-gamma
Protein Serine-Threonine Kinases
Receptor, Transforming Growth Factor-beta Type II