Interleukin 19

IL19
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1N1F
Identifiers
Aliases	IL19, IL-10C, MDA1, NG.1, ZMDA1, Interleukin 19, IL-19
External IDs	OMIM: 605687 MGI: 1890472 HomoloGene: 17813 GeneCards: IL19
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q32.1 Start 206,770,764 bp[1] End 206,842,981 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 E4 Start 130,932,656 bp[2] End 130,940,115 bp[2]
Gene ontology Molecular function • cytokine activity • GO:0001948 protein binding Cellular component • extracellular region • extracellular space Biological process • negative regulation of extrinsic apoptotic signaling pathway • positive regulation of apoptotic signaling pathway • positive regulation of intrinsic apoptotic signaling pathway • signal transduction • reactive oxygen species metabolic process • apoptotic process • immune response • regulation of signaling receptor activity • cytokine-mediated signaling pathway • negative regulation of low-density lipoprotein particle clearance Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	29949	329244
Ensembl	ENSG00000142224	ENSMUSG00000016524
UniProt	Q9UHD0	Q8CJ70
RefSeq (mRNA)	NM_013371 NM_153758 NM_001369605 NM_001393490 NM_001393491	NM_001009940 NM_001355135
RefSeq (protein)	NP_037503 NP_715639 NP_001356534	NP_001009940 NP_001342064
Location (UCSC)	Chr 1: 206.77 – 206.84 Mb	Chr 1: 130.93 – 130.94 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[5]

Structure[]

The IL-19 gene contains 7 exons. Secreted IL-19 protein is made from 159 amino acids in an alpha-helix structure.^[5]

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.).^[6]

A demonstration of IL-19 binding to the IL20 Receptor on the surface of immune cells to regulate cytokine expression

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).^[7][8][9]

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.^[9] The IL-19 induced macrophage polarization reduces the pro-inflammatory cytokines produced by M1 macrophages, thus limiting the magnitude of the inflammatory response.

A demonstration of the protective effect of IL-19 in vascular disease by decreasing immune cell recruitment to inflamed tissue and reducing oxidative stress.

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.^[10]

Adhesion molecule regulation[]

IL-19 suppresses the expression of RNA-binding protein HuR, an mRNA stability factor.^[11] 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.^[12]

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).^[12] 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^[13] In contrast, Th2 cells secrete IL-4 and IL-10 and downregulate IFN-γ.^[13] 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.^[14] 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.

References[]

External links[]

• Overview of all the structural information available in the PDB for UniProt: Q9UHD0 (Interleukin-19) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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