Innate and Adaptive Interleukin-17–producing Lymphocytes in Chronic Inflammatory Lung Disorders

Abstract

During T-cell receptor activation in a particular cytokine environment, naive CD4+ T cells may differentiate into lineages defined by their pattern of cytokine production and transcription factors: T helper type 1 (Th1), Th2, Th17, and Th22 cells; follicular helper T cells; and inducible regulatory T cells. Th17 cells have been recognized as a distinct lineage of Th cells, and associations between IL-17 and human disease have been known somewhat longer. It would be an oversimplification to restrict IL-17 to Th17 cells. Indeed, IL-17 is also expressed by other cells including IL-17-producing γδ T (γδ T-17) cells, natural killer T-17 cells, and IL-17-producing lymphoid tissue-induced cells. IL-17 was cloned in 1995 as a cytokine expressed by T cells, exerting inflammatory effects on epithelial, endothelial, and fibroblast cells. IL-17 is a solid link between innate and adaptive immunity and can exert both beneficial and deleterious effects. The discovery of IL-17 T cells has provided exciting new insights into host defense, immunoregulation, and autoimmunity. Unquestionably, data from mouse models have contributed enormously to our insight into immunological mechanisms. However, because of numerous differences between murine and human immunology, data obtained in mice are not simply interchangeable. We review IL-17 T cells exclusively in the human situation and more specifically their potential role in respiratory diseases. The advances in our understanding of IL-17 regulation offer opportunities to dissect the human IL-17 system and to reflect on the clinical presentation of lung diseases. More importantly, the IL-17 system allows us to speculate on new therapeutic opportunities. Some results have been previously reported in an abstract.