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IL-10 Family Proteins

IL-10 (Interleukin-10) is a family of interleukins including IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29. The IL-10 family proteins are all members of the class II cytokine receptor family. All receptors are heterodimers composed two alpha and two beta chains that form the receptor signalling complex. These class II cytokine receptors are characterised by the presence of two fibronectin Type III domains in their extracellular region. These are globular molecules that consist of seven beta-strands which subsequently form two beta sheets and are usually associated with cell surface adhesion molecules. The binding of IL-10 family proteins to its class II cytokine receptor family results in the signalling of STAT3, a transcription factor, via the phosphorylation of the cytoplasmic tails of the IL-10 receptors by JAK1 and Tyk2.

The structure of all members of the IL-10 family members is conserved. They all have a similar alpha-helix structure. It is suggested that all six members of the IL-10 protein family possess six alpha-helices. The membership is based on conserved cysteine positions in their receptor sequence.

IL-10 also known as human cytokine synthesis inhibitory factor (CSIF) and is a potent anti-inflammatory cytokine. It strongly inhibits the production of pro-inflammatory cytokines such as IFNγ, TNF-α, IL-1β, IL-6 in several types. It is predominantly produced by monocytes and to a lesser extent regulatory T cells, T helper cells and activated B cells. The cytokine, IL-10 also prevents dendritic cell maturation by inhibiting IL-12 expression. Additionally, IL-10 also inhibits expression of MHC and co-stimulatory molecules which are important for cell-mediated immunity. Additionally, IL-10 also inhibits the production of IFNγ from CD8+ T cells which further dampens a pro-inflammatory immune response.

The other members of the IL-10 family have not been characterised as extensively as IL-10. IL-19 is also mainly produced by monocytes and less by B lymphocytes. Increased production of IL-19 is stimulated by the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) produced by gram-negative bacteria. IL-19 increases the production of cytokines produced by T helper 2 cells (Th2) and also stimulates the production of IL-10.

IL-20 is another member of the IL-10 family of proteins. This cytokine is produced by activated keratinocytes in the skin and monocytes. The main function of IL-20 is to regulates proliferation and differentiation of keratinocytes, which are cells of the epidermis. This cytokine plays a role in psoriasis, as the receptor for IL-20 is upregulated on keratinocytes in psoriatic skin.

IL-22 is produced by a variety of immune cells at a site of infection.These include Th1, Th22 and Th17 cells, γδ T cells, natural killer T cells (NKT), neutrophils and macrophages.IL-22 is involved in cell survival, proliferation and synthesis of antimicrobials that have infected stromal and epithelial cells. Therefore IL-22 aids in wound healing and defence against microbes.

IL-24 is a secreted cytokine that is produced by myeloid cells, lymphoid cells and epithelial cells in response to cytokine stimulation. Its main function is in wound healing, by inhibiting proliferation of keratinocytes during infections of the skin to decrease inflammation in the surrounding area.

IL-26 is another member of the IL-10 family proteins and is mainly produced by Th17 cells. It functions as an antimicrobial molecule by promoting immune sensing of bacterial and host cell death. It also kills extracellular pathogens by forming pores in their membranes leading to cell lysis and death. Furthermore, IL-26 forms complexes with bacterial DNA and host DNA released by dying bacteria and host cells. These complexes trigger the production of type I interferon by dendritic cells via the activation of toll-like receptor 9.

IL-28 and IL-29 are the final members of the IL-10 family. They are different to the other members of the family as they also belong to the Type III Interferon group, which play an important role in the defence against viruses. IL-28 and IL-29 receptors signals through JAK-STAT pathways which leads to the expression of activated interferon-stimulated genes and production of antiviral proteins. IL-29 is dominantly produced in virally infected epithelial cells of the respiratory, gastrointestinal and urogenital tracts whereas IL-28 is mainly produced by keratinocytes and melanocytes.

ELISA Genie provides a range of ELISA kits for the research of IL-10 and its family members.

IL-10 Family Ligands

IL-10 Family Receptors

IL-10 Family Signalling Molecules

Resources

Cytokines and Growth Factors

Immunology