Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
Nat Immunol. 2011 Jun 20;12(7):597-606. doi: 10.1038/ni.2059.
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 (T(H)1) 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 T(H)1 differentiation program. T-bet induces the production of interferon-γ (IFN-γ) and orchestrates the T(H)1 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.
针对微生物攻击，免疫防御机制的激活必须强大且能够适应特定类型病原体的攻击。细胞内微生物感染会引发 1 型炎症反应，其特征是 T 辅助细胞 1（T(H)1）细胞向感染部位迁移，在感染部位负责招募和激活巨噬细胞。1 型炎症反应的核心是转录因子 T-bet，它是 T(H)1 分化程序的关键调节因子。T-bet 诱导干扰素-γ（IFN-γ）的产生，并通过调节趋化因子和趋化因子受体的表达来协调 T(H)1 细胞迁移程序。然而，1 型炎症反应的严密调控对于预防免疫病理学和器官特异性自身免疫的发展至关重要。在这篇综述中，我们讨论了 T-bet 表达如何驱动自身免疫和炎症过程，以及其在体内的功能必须如何精细平衡以避免疾病。
