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One way to pathogenesis, many ways to homeostasis

Cellular & Molecular Immunology volume 10, pages 2–3 (2013)Cite this article

CD4 T cells play central roles in both immune response and regulation. They can either serve as the mediators of adaptive immune response against infections, or act as gate keepers to maintain immune homeostasis. Upon activation by antigens, naive T cells proliferate and differentiate into different T helper (Th) cells with distinct effector functions. Th1 cells, induced by transcription factor T-bet and produce interferon-γ, are crucial for clearing intracellular pathogens. In contrast, IL-4 expressing Th2 cells driven by GATA-3 are responsible for the clearing of extracellular pathogens. Th17 cells, an additional subset of T cells expressing transcription factor RORγt and cytokine IL17, are considered as the main drivers of autoimmune tissue injury. On the contrary, CD4+FoxP3+ regulatory T (Treg) cells, which can be generated either in the thymus or in the peripheral in respond to chronic challenges, are known to play key roles in maintaining immunological homeostasis and the control of autoimmune deviation or diseases. In a recent issue of Nature Immunology, two independent studies from Harvard Medical School described the transcriptional signature of effector Th17 and Treg cells and unveiled very different mechanisms in instructing these two cell types.1,2

Th17 cells are characterized by their capacities to produce IL-17A, IL-17F, IL-21 and IL-22. In vivo, these cells are present at the site of tissue inflammation in many autoimmune diseases and are thought to be the critical drivers of autoimmune tissue inflammation and damage. In vitro, IL-17 expressing cells can be differentiated by a combination of the cytokines transforming growth factor (TGF)-β1 and IL-6. However, Th17 cells induced by TGF-β1 and IL-6 in vitro do not readily induce autoimmune inflammation and need additional exposure to another cytokine IL-23 to become pathogenic.3

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Authors and Affiliations

  1. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China

    Linrong Lu & Jianli Wang

  2. Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou, China

    Linrong Lu

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  1. Linrong Lu
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  2. Jianli Wang
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Correspondence to Linrong Lu or Jianli Wang.

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Lu, L., Wang, J. One way to pathogenesis, many ways to homeostasis. Cell Mol Immunol 10, 2–3 (2013). https://doi.org/10.1038/cmi.2012.51

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