Interluekin-17A (IL17A)

Abstract

The discovery of the key roles of interleukin-17A (IL-17A) and IL-17A producing cells in inflammation, autoimmune diseases and host defense has led to the experimental targeting of the IL-17A pathway in animal models of diseases as well as in clinical trials in humans. These therapeutic agents include biological products that target IL-17A and IL-23, an upstream regulator of IL-17A production. IL-17A producing T helper cells (Th17 cells) are a distinct lineage from the Th1 and Th2 CD4+ lineages and have been suggested to represent a good drug target in certain inflammatory conditions. Targeting IL-17A has been proven to be a good approach as anti-IL-17A is FDA approved for the treatment of psoriasis in 2015. In host defense, IL-17A has been shown to be mostly beneficial against infection caused by extracellular bacteria and fungi. This review will overview the discovery of IL-17A, the receptors used by this cytokine and its role in mucosal immunity and inflammation.

Keywords: Cancer; Inflammation; Interleukin-17A; Neutrophil.

Figure 1. Schematic illustration of signaling pathway that involves IL-17A in inflammatory diseases

Naïve CD4 T cells differentiate into IL-17 producing T cells under the cytokine environment including TGF-β, IL-6, IL-1β and IL-23. Th17 differentiation is controlled by transcription factors including RORA, RORC and STAT3. Type 3 innate lymphoid cell (ILC3) and γδ-T cell can also produce IL-17 in respond to IL-1β and IL-23 stimulation. IL-17A acts on structural cells such as epithelial cells, fibroblasts and keratinocytes in various tissue including skin, gut as well as lung. Structural cells that express IL-17 receptor produce inflammatory cytokines such as G-CSF and IL-6 as well as chemokines to attract neutrophils and macrophage to the inflamed tissues. These inflammatory cells can both clear the infection and initiate pathogenic inflammation.