[Frontiers in Bioscience 15, 986-1006, June 1, 2010]

[Frontiers in Bioscience 15, 986-1006, June 1, 2010]

Th 17 cells interplay with Foxp3⁺ Tregs in regulation of inflammation and autoimmunity

Jietang Mai, Hong Wang, Xiao-Feng Yang

Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Old Th1-Th2 paradigm versus new multi-subset paradigm: 3.1. The Th1-Th2 paradigm's crisis; 3.2. New CD4+ Th subsets - Tregs, Th17, Th9, Tfh, IL-10 IFN-gamma-secreting CD4+ T cells and CD4+CD28null T cells
4. Structural features of IL-17 family cytokines
5. Th17 cells
6. Effects of IL-17 on various cell types and tissues: 6.1. Synovial stromal cells; 6.2. Fibroblasts; 6.3. Endothelial cells; 6.4. Vascular smooth muscle cells (VSMCs); 6.5. Monocytic cells and macrophages; 6.6. Structural lung cells
7. IL-17 receptors and signaling pathways: 7.1. IL-17 receptor family; 7.2. IL-17 receptor complex components; 7.3. IL-17 receptor signaling
8. Th17-mediated inflammations: 8.1. Experimental autoimmune encephalomyelitis (EAE)/multiple sclerosis; 8.2. Inflammatory skin disease in mice and psoriasis in humans; 8.3. Inflammatory bowel disease (IBD); 8.4. Experimental arthritis/rheumatoid arthritis; 8.5. Atherosclerosis; 8.6. Diabetes
9. Protective mechanisms of IL-17 in infections
10. Th17 cells interplay with Tregs: 10.1. Updates of Tregs; 10.2. Reciprocally interconnected Th17 and Tregs; 10.3. Inhibition of Th17 by Tregs
11. Conclusions
12. Acknowledgements
13. References

1. ABSTRACT

T helper 17 cells (Th17) are a new CD4⁺ T helper subset that has been implicated in inflammatory and autoimmune diseases. Th17, along with CD4⁺CD25^high Foxp3⁺ regulatory T cells (Tregs) and other new T helper subsets, have expanded the Th1-Th2 paradigm. Although this new eight-subset paradigm significantly improved our understanding on the differentiation and regulation of CD4⁺ T helper subsets, many questions remain to be answered. Here we will briefly review the following issues: a) Old Th1-Th2 paradigm versus new multi-subset paradigm; b) Structural features of IL-17 family cytokines; c) Th17 cells; d) Effects of IL-17 on various cell types and tissues; e) IL-17 receptor and signaling pathways; f) Th17-mediated inflammations; and g) Protective mechanisms of IL-17 in infections. Lastly, we will examine the interactions of Th17 and Treg in autoimmune diseases and inflammation: Th17 cells interplay with Tregs. Regulation of autoimmunity and inflammation lies in the interplays of the different T helper subsets, therefore, better understanding of these subsets' interactions would greatly improve our approaches in developing therapy to combat inflammatory and autoimmune diseases.