The Special Relationship in the Development and Function of T Helper 17 and Regulatory T Cells

Abstract

T helper 17 (Th17) cells play an essential role in the clearance of extracellular pathogenic bacteria and fungi. However, this subset is critically involved in the pathology of many autoimmune diseases, e.g., psoriasis, multiple sclerosis, allergy, rheumatoid arthritis, and inflammatory bowel diseases in humans. Therefore, Th17 responses need to be tightly regulated in vivo to mediate effective host defenses against pathogens without causing excessive host tissue damage. Foxp3+ regulatory T (Treg) cells play an important role in maintaining peripheral tolerance to self-antigens and in counteracting the inflammatory activity of effector T helper cell subsets. Although Th17 and Treg cells represent two CD4+ T cell subsets with opposing principal functions, these cell types are functionally connected. In this review, we will first give an overview on the biology of Th17 cells and describe their development and in vivo function, followed by an account on the special developmental relationship between Th17 and Treg cells. We will describe the identification of Treg/Th17 intermediates and consider their lineage stability and function in vivo. Finally, we will discuss how Treg cells may regulate the Th17 cell response in the context of infection and inflammation, and elude on findings demonstrating that Treg cells can also have a prominent function in promoting the differentiation of Th17 cells.