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

Speaker: 張振田                   Place: 601 room

Commentator: 凌斌 老師            Time: 2005/09/14 14:10-15:00    

Abstract:

  To combat the diversity of infectious pathogens, host organisms have evolved different kinds of innate and adaptive immune response.  For intracellular pathogens, macrophage, dendritic cell (DC), NK cell and naïve T cell are the main cellular components, while, interleukin 12 (IL-12) and interferon γ(IFN-γ) are the major secreted cytokines in early immune response.  The early responses enhance the bactericidal activity of macrophages and, thereafter, induce antigen specific Th1 response.  Owing to the marked tissue damage effect of Th1 response, the development of this strong immune response is tightly controlled by various mechanisms.  The IFN-γ secreted by the innate immune cells during the early phase of infection is negatively regulated by IL-10 and transforming growth factor-β(TGF-β).  However, the molecular mechanism that links innate and Th1 response was not fully understood.  In this study, the authors used a dominant negative form of TGF-βreceptor II under control of the CD11c promoter(CD11c-dnTGFβRII) in both NK cell and DC compartments in a leishmania infection model to study the role of TGF-β in the innate and Th1 response.  The results showed that blockade of TGF-β signaling in NK cells caused the accumulation of a large pool of NK cells which secret copious IFN-γ and lead to Th1 differentiation and hence protection from leishmania infection.  In contrast, blockade of TGF-β signaling in dendritic cells did not affect dendritic cell homeostasis or IL-12 production.  This demarcated function of TGF-β in NK cells versus dendritic cells had not been described previously.  It indicates that TGF-β signaling is a checkpoint event that tightly controls Th1 development through regulation of IFN-γ production by NK cells.

References:

1.Laouar,Y., Sutterwala,F.S., Gorelik,L., and Flavell,R.A. (2005). Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma. Nat. Immunol. 6, 600-607.

2.Lieberman,L.A. and Hunter,C.A. (2002). Regulatory pathways involved in the infection-induced production of IFN-gamma by NK cells. Microbes. Infect. 4, 1531-1538.