EditorialShifting the imbalance from Th1/Th2 to Th17/treg: The changing rheumatoid arthritis paradigm
Introduction
Knowledge recently acquired in the field of immunopathology has radically changed the paradigm for rheumatoid arthritis (RA). The pathogenesis of this destructive disease was classically viewed as involving two hierarchical systems, governing inflammation and autoimmunity, respectively. The key players in this paradigm were the pro-inflammatory cytokine TNFα and the Th1 subset of helper T-cells [1], [2]. The identification of Th17T-cells and regulatory T-cells (Treg) has challenged this paradigm for the first time in two decades [3].
Section snippets
The classical paradigm: rheumatoid arthritis is a Th1-driven disease
CD4 + T-cells, or T-helper cells (Th), are at the hub of this paradigm, which was developed in the 1980s. Many studies, most of which relied heavily on animal experiments, led to the belief that RA was a Th1-driven disease [4]. The Th1 phenotype is associated with inflammation, whereas the Th2 phenotype combats inflammation to some extent. The characteristic Th1 cytokine is interferon-γ (IFN-γ). Differentiation of naive T-cells into Th1 cells is accompanied with the production of inflammatory
Is there a Th17/Treg balance?
The missing link may be the Th17, which is a key effector in the immune response. Treg cells orchestrate the overall immune response. A naive T-cell, once activated, follows one of a variety of differentiation pathways, which confer either effector or regulator functions.
Effector T-cells contribute to normal defense responses. Three effector T-cell phenotypes have been identified (Fig. 2).
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Th1: the Th1 phenotype results from expression of transcription factors such as T-bet and STAT4. Th1 cells
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