The activation of immune-defense mechanisms in response to a microbial attack must be robust and appropriately tailored to fight particular types of pathogens. Infection with intracellular microorganisms elicits a type 1 inflammatory response characterized by mobilization of T helper type 1 (TH1) cells to the site of infection, where they are responsible for the recruitment and activation of macrophages. At the center of the type 1 inflammatory response is the transcription factor T-bet, a critical regulator of the TH1 differentiation program. T-bet induces the production of interferon-γ (IFN-γ) and orchestrates the TH1 cell–migratory program by regulating the expression of chemokines and chemokine receptors. However, tight regulation of the type 1 inflammatory response is essential for the prevention of immunopathology and the development of organ-specific autoimmunity. In this review, we discuss how T-bet expression drives autoaggressive and inflammatory processes and how its function in vivo must be delicately balanced to avoid disease.
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Supported by the US National Institutes of Health (P01 NS038037 and CA112663 to L.H.G.), the Danone Group and the Cancer Research Institute (V.L.).
L.H.G. is a member of the board of directors of and holds equity in Bristol Myers Squibb.
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