Th17 cells in human disease

Abstract

Our understanding of the role of T cells in human disease is undergoing revision as a result of the discovery of T-helper 17 (Th17) cells, a unique CD4(+) T-cell subset characterized by production of interleukin-17 (IL-17). IL-17 is a highly inflammatory cytokine with robust effects on stromal cells in many tissues. Recent data in humans and mice suggest that Th17 cells play an important role in the pathogenesis of a diverse group of immune-mediated diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and asthma. Initial reports also propose a role for Th17 cells in tumorigenesis and transplant rejection. Important differences, as well as many similarities, are emerging when the biology of Th17 cells in the mouse is compared with corresponding phenomena in humans. As our understanding of human Th17 biology grows, the mechanisms underlying many diseases are becoming more apparent, resulting in a new appreciation for both previously known and more recently discovered cytokines, chemokines, and feedback mechanisms. Given the strong association between excessive Th17 activity and human disease, new therapeutic approaches targeting Th17 cells are highly promising, but the potential safety of such treatments may be limited by the role of these cells in normal host defenses against infection.

Figures

Fig. 1. Th17 cells and immune-mediated diseases

Schematic diagram showing the central role played by human Th17 cells in four types of immune-mediated inflammatory conditions. The middle diamond represents effects that occur outside the lesions either in lymph nodes or systemically. Solid arrows indicate proven associations, while dashed arrows indicate likely associations based on effects commonly found in other diseases. Shared features include induction of Th17 cells by inflammatory cytokines (IL-1β, IL-6, and IL-23) elicited by dendritic cells, macrophages, osteoblasts, or brain microglial cells, either in local lesions or in draining lymph nodes. Common effector functions of Th17-derived IL-17 and IL-22 include induction of chemokines and pro-inflammatory cytokines from stromal cells, and stimulation of matrix metalloproteinases from macrophages and stromal cells. Organ-specific effects such as osteoclastogenesis, disruption of the blood brain barrier, and mucus hypersecretion are described further in the text.