Cytokines & Chemokines

The human IL-13 cDNA encodes a 132 amino acid protein containing a proposed 20 amino acid signal peptide. Human IL-13 shares approximately 30% amino acid sequence homology to human IL-4 and the two cytokines exhibit overlapping biological activities. Human IL-13 is produced by activated Th0, Th1-like Th2-like and CD8 T cells. Similarly to IL-4, IL-13 has multiple effects on the differentiation and functions of monocytes/macrophages. IL-13 can suppress the cytotoxic functions of monocytes/macrophages. It can also suppress the production of proinflammatory cytokines and upregulate the production of IL-1ra by monocytes/macrophages.

Human IL-17F is synthesized as a 153 aa precursor with a 20 aa signal sequence and a 133 aa mature region. Like IL-17A, IL-17F contains one potential site for N-linked glycosylation. IL-17A and IL-17F share 50% aa sequence identity. IL17-F homodimer is produced by an activated subset of CD4+ T cells, termed Th17. IL17-F has been shown to stimulate proliferation and activation of T-cells and PBMCs. IL-17F also regulates cartilage matrix turnover and inhibits angiogenesis.

Human IL-17F is synthesized as a 153 aa precursor with a 20 aa signal sequence and a 133 aa mature region. Like IL-17A, IL-17F contains one potential site for N-linked glycosylation. IL-17A and IL-17F share 50% aa sequence identity. IL17-F homodimer is produced by an activated subset of CD4+ T cells, termed Th17. IL17-F has been shown to stimulate proliferation and activation of T-cells and PBMCs. IL-17F also regulates cartilage matrix turnover and inhibits angiogenesis.

IL-20 is a member of the IL-10 family of regulatory cytokines which includes IL-10, IL-19, IL-20, IL-22, IL-24 and IL-26. Members of this family share partial homology in their amino acid sequences but they are dissimilar in their biological functions. IL-20 is a hematopoietic growth factor capable of stimulating colony formation by CD34+ multipotential progenitors, but not by other progenitor cells. IL-20 signals through a receptor system composed of type I IL-20R-α and type II IL-20R-β. Over-expression of IL-20 in keratinocytes expressing both receptor subunits has been implicated in the induction of inflammatory skin disease.

IL-20 is a member of the IL-10 family of regulatory cytokines which includes IL-10, IL-19, IL-20, IL-22, IL-24 and IL-26. Members of this family share partial homology in their amino acid sequences but they are dissimilar in their biological functions. IL-20 is a hematopoietic growth factor capable of stimulating colony formation by CD34+ multipotential progenitors, but not by other progenitor cells. IL-20 signals through a receptor system composed of type I IL-20R-α and type II IL-20R-β. Over-expression of IL-20 in keratinocytes expressing both receptor subunits has been implicated in the induction of inflammatory skin disease.

IL-21 is a pleiotropic cytokine produced by CD4+ T cells in response to antigenic stimulation. Its action generally enhances antigen-specific responses of immune cells. The biological effects of IL-21 include induction of differentiation of T-cells-stimulated B-cells into plasma cells and memory B-cells, stimulation (in conjuction) with IL-4 of IgG production, and induction of apoptotic effects in naïve B-cells and stimulated B-cells in the absence of T-cell signaling. Additionally, IL-21 promotes the anti-tumor activity of CD8+ T-cells and NK cells. IL-21 exerts its effect through binding to a specific type I cytokine receptor, IL-21R, which also contains the gamma chain (γc) found in other cytokine receptors including IL-2, IL-4, IL-7, IL-9 and IL-15. The IL-21/IL-21R interaction triggers a cascade of events which includes activation of the tyrosine kinases JAK1 and JAK3, followed by activation of the transcription factors STAT1 and STAT3.

Human IL-31 is a T-cell derived cytokine that shares several structural and functional characteristics with IL-6, Oncostatin M, LIF, and Cardiotrophin-1. It signals through a receptor complex comprised of GPL (GP130-like, IL-31RA) and OSMR (Oncostatin M receptor). GPL/OSMR signaling is a strong activator of STAT3 and STAT5, and can also activate STAT1, Jak1, and Jak2 signaling pathways. IL-31 regulated immune responses have been implicated in skin physiology and inflammatory skin diseases.

Human IL-31 is a T-cell derived cytokine that shares several structural and functional characteristics with IL-6, Oncostatin M, LIF, and Cardiotrophin-1. It signals through a receptor complex comprised of GPL (GP130-like, IL-31RA) and OSMR (Oncostatin M receptor). GPL/OSMR signaling is a strong activator of STAT3 and STAT5, and can also activate STAT1, Jak1, and Jak2 signaling pathways. IL-31 regulated immune responses have been implicated in skin physiology and inflammatory skin diseases.

TSLP is a hemopoietic protein that is expressed in the heart, liver and prostate. TSLP overlaps biological activities with IL-7 and binds with the heterodimeric receptor complex consisting of the IL-7R alpha chain (IL-7Rα) and the TSLP-specific chain (TSLPR). Like IL-7, TSLP induces phosphorylation of STAT3 and STAT5, but uses kinases other than the JAKs for activation. TSLP prohibited apoptosis and stimulated growth of the human acute myeloid leukemia (AML)-derived cell line MUTZ3. It induces the release of T cell-attracting chemokines TARC and MDC from monocytes and activates CD11c(+) dendritic cells (DCs). TSLP activated DCs primed naive T cells to produce the proallergic cytokines (IL-4, IL-5, IL-13, TNFα) while down-regulating IL-10 and IFN-γ suggesting a role in initiating allergic inflammation.