An Update on Interleukin-9: From Its Cellular Source and Signal Transduction to Its Role in Immunopathogenesis

Abstract

Interleukin-9 (IL-9) is a pleiotropic cytokine and was primarily studied in the context of T helper 2 (T_H2)-associated immuno-pathological conditions such as asthma and parasitic infections. There was a paradigm shift in the biology of IL-9 after the recent discovery of T_H9 cells, a new subtype of T_H cells which secrete IL-9 in copious amounts. This has resulted in renewed interest in this cytokine, which was neglected since discovery because it was considered it to be just another T_H2 cytokine. Recent studies have shown that it has multiple cellular sources and is critically involved in the immune-pathogenesis of inflammatory diseases and in guarding immune tolerance. In this review, we will discuss its discovery, gene organization, cellular sources, and signaling pathways. Especially, we will give an update on the recent development regarding its relevance in the immune pathogenesis of human diseases.

Keywords: inflammatory diseases; interleukin-9; signal transduction.

Figure 1

IL-9 mediated signal transduction. IL-9 binding results in the formation the IL-9R heterocomplex, which induces phosphorylation of JAKs. Phosphorylated JAKs then activate signaling intermediates of JAK-STAT, IRS—PI3 kinase, and MAPK pathways. (STAT—Signal Transducer and Activator of Transcription; IRS—insulin receptor substrate; MAPK—Mitogen-Activated Protein Kinase; PI3-K—Phosphatidylinositol-3 Kinase having two subunits, p110 and p85; PDK—PI3-K dependent kinase; PIAS—Protein Inhibitors of Activated STATs; SOCS—Suppressors Of Cytokine Signaling).

Figure 2

Various cellular sources of IL-9.