The potential role of interleukin-17 in severe asthma

Abstract

Asthma has long been characterized as a disease of dysregulated T-helper type 2 immune responses to environmental allergens. Clinical studies suggest that asthma is a heterogeneous disorder with distinct types of inflammatory processes. Accumulating evidence suggests that aberrant interleukin (IL)-17 production is a key determinant of severe forms of asthma. However, the identity of IL-17-producing cells and the factors regulating IL-17 production during the course of allergic inflammation remain elusive. In this review, we summarize the potential IL-17-producing cells and their involvement in the inflammatory responses that mediate distinct features of asthma. The role of proinflammatory cytokines and the complement pathway in regulating the generation of IL-17-producing T cells is also discussed. Understanding the biology of IL-17 in the context of allergic inflammation may be informative in the development of novel approaches to the diagnosis and treatment of asthma.

Fig. 1. The development of IL-17-producing T cells and the severity of asthma

Upon exposure to allergens and infectious agents, dendritic cells activated by TSLP (thymic stroma lymphopoietin) or anaphylatoxin C3a can induce naïve T cells to differentiate into TH2 or TH17 cells, respectively. Depending on the inflammatory signals in the microenvironment, local TH2 memory/effector cells may acquire distinct inflammatory properties to become IL-17-producing cells that promote severity of asthma.