Interleukin 19

Interleukin 19 (IL-19) is a protein that belongs to the IL-10 cytokine subfamily. Human IL-19 is encoded by the IL-19 gene located on chromosome 1.
Structure.
The IL-19 gene contains 7 exons. Secreted IL-19 protein is made from 159 amino acids in an alpha-helix structure.
Function.
IL-19 is an immunosuppressive cytokine that is responsible for both cell type-specific and system-specific down-regulation of inflammation. IL-19 interacts with both immune cells (macrophages, T cells, B cells) and non-immune cells (endothelial cells and brain resident glial cells, etc.).
Induction of immune cells polarization.
IL-19 is homologous to interleukin 20 (IL-20) and thus is able to bind the interleukin-20 receptor complex. IL-19 binding the dimer receptor IL20R leads to activation of the JAK/STAT signaling pathway. Following STAT protein entering the nucleus of a T-helper cell, the cell differentiates into a less inflammatory T-helper 2 cells through downregulation of interferon gamma (IFN-γ) and upregulation of interleukin 4(IL-4) and interleukin 10 (IL-10).
Macrophages can also be polarized and have distinct functional phenotypes after receiving specific signals. When IL-19 binds to the IL-20R receptors on macrophages, it induces expression of IL-10, promoting the macrophage polarization from the inflammatory M1 type to an anti-inflammatory phenotype M2. The IL-19 induced macrophage polarization reduces the pro-inflammatory cytokines produced by M1 macrophages, thus limiting the magnitude of the inflammatory response. 
Protection against vascular inflammation.
IL-19 is not detectable in healthy arteries, but frequently observed in damaged vessels. After receiving damage, IL-19 is secreted by vascular cells to recover from inflammation and protect tissue against further damage. 
Adhesion molecule regulation.
IL-19 suppresses the expression of RNA-binding protein HuR, an mRNA stability factor. HuR is responsible for stabilizing mRNA that codes for adhesion molecules excreted by activated macrophages, and later allow for neutrophil movement into peripheral or cardiac tissue. Through downregulation of this factor, fewer adhesion molecules are translated and expressed in the endothelial cell lined up in blood vessels. With fewer neutrophils entering cardiac tissue, IL-19 protects the vascular tissue from damage related to inflammatory processes.
Reduction of oxidative stress.
IL-19 upregulates the expression of heme oxygenase-1 (HO-1) and reduces reactive oxygen species in human vascular smooth muscle cells. 
Immune cell polarization.
The induction of anti-inflammatory cytokines (IL-10 and IL-4) and downregulating pro-inflammatory cytokines (IFN-γ) pushes a T helper cell away from T-helper 1 (Th1) to T-helper 2 (Th2). During vascular infection, Th1 is the predominant T cells population and expresses interferon IFN-γ, tumor necrosis factor-α, and other pro-inflammatory cytokines, leading to vessel tissue damage In contrast, Th2 cells secrete IL-4 and IL-10 and downregulate IFN-γ. This dampens the inflammatory response by inhibiting pro-inflammatory gene expression. Additionally, macrophages receiving the IL-19 signal are polarized from M1 (pro-inflammatory) to M2 (anti-inflammatory).
Neuroprotection.
The resident glial cells of the central nervous system participate in neuroinflammation initiation and regulation. Glial cells such as microglia and astrocytes produce inflammatory cytokines in response to foreign antigens and then produce immunosuppressive cytokines to resolve inflammation.  IL-19, secreted by astrocytes, functions as an immunosuppressive signal in a manner of delayed kinetics of induction. The induction of IL-19 often occurs after immune response initiation as a secondary, anti-inflammatory, neuroprotective regulation to limit the inflammation. Astrocytes produce IL-19 to interact with cells expressing IL-20 receptors (microglia etc.), in order to regulate cytokine secretion, which includes reducing the production of pro-inflammatory cytokines such as IL-6 TNF-α. 
IL-10 family.
Interleukin-19 is a cytokine that belongs to the IL-10 family of cytokines along with several other interleukins including IL-10, IL-20, IL-22, IL-24, IL-26, and several virus-encoded cytokines. It signals through the same cell surface receptor (IL-20R) that is used by IL-20 and IL-24. 