Interleukin 26
Ensembl |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
UniProt |
| ||||||||
RefSeq (mRNA) |
| ||||||||
RefSeq (protein) |
| ||||||||
Location (UCSC) | Chr 12: 68.2 – 68.23 Mb | n/a | |||||||
PubMed search | [2] | n/a |
View/Edit Human |
Interleukin-26 (IL-26) is a protein that in humans is encoded by the IL26 gene.[3][4][5]
IL-26 is the most recently identified member of the
Gene organization and protein structure
The IL26 gene is conserved in various vertebrates, but it is curiously absent in mice and rats. Paralogs of this gene have been identified in several non-mammalian species.[9] The human gene is located on chromosome 12 (12q15), between the genes encoding IL-22 and IFNγ,[10] and composed of five exons separated by three introns. This genomic cluster of genes encoding IL-22, IL-26, and IFNγ is present among all vertebrates.[11]
IL-26 is a 171-amino acid protein that exhibits six alpha helices connected by loops and four conserved cysteine residues. Endogenous IL-26 is expressed as a 36 kDa homodimer.[4] Originally named AK155, IL-26 was categorized in the IL-10 cytokine family due to sequence homology and secondary structure similarities.
Expression
The IL-26 expression was initially discovered in human HVS-transformed T cells.[6] Since then it was confirmed that T helper 1 cells and Th17 memory CD4+ cells are the major sources of IL-26. More accurately, IL-26 is expressed by pro-inflammatory IL-17 producing T cells in chronically inflamed tissues.[12][13][14] Co-expression of IL-17, IL-22, and IL-26 de facto defines the phenotype of human Th17 cells. Furthermore, CD26+ CD4+ T cells produce IL-26 in a model of graft-versus-host disease (GvHD).[15] CD4+ T cells polarized toward a regulatory phenotype (Treg), naïve CD4+ T cells, and T helper 2 cells show low or no expression of IL-26.[16]
It remains unclear whether IL-26 monocytes and macrophages express IL-26. Some studies showed there is no expression,[16] whereas other studies inconsistently reported constitutive expression at a low level in monocytes,[17] and the secretion of IL-26 by lung alveolar macrophages locally exposed to endotoxin.[18] The IL-26 expression is also present in NK cells,[16] especially NKp44+ human NK cell subset localized in mucosa-associated lymphoid tissue express substantial amounts of IL-26.[19] Very low IL-26 expression was reported in human herpesvirus 8-transformed B cells.[4]
Regarding non-immune cells, IL-26 expression was detected in primary bronchial epithelial cells from healthy individuals.[16] Pathologically, fibroblasts harvested from the inflamed synovia of patients with rheumatoid arthritis constituted the main source of IL-26.[14]
Receptors
IL-26R heterodimer, a conventional receptor for IL-26, consists of two chains – IL-10R2, and IL-20R1. there is a possibility that additional IL-26 receptors exist.
Ligand binding by functional IL-26 receptor complex results in the initiation of a signal transduction pathway involving receptor-associated Janus tyrosine kinases Jak1 and Tyk2. IL-20R1 interacts with Jak1, and IL-10R2 is associated with Tyk2. Ligand-induced heterodimerization of receptor chains promotes cross-activation of Janus kinases, which phosphorylate receptor intracellular domains, leading to the activation of STAT protein family intracellular transcription factors STAT1 and STAT3. In addition, IL-26 activates extracellular signal-regulated kinases (ERK)-1/2, c-Jun N-terminal kinase (JNK), mitogen-activated protein kinases (MAPKs), and protein kinase B (PKB).[7]
While IL-10R2 is expressed on a wide variety of tissues, the expression of IL-20R1 is limited only to some tissues.[21] Thus, the ability to respond to IL-26 is restricted by the expression of IL-20R1 subunit.
Role
Interleukin 26 (IL-26) is an inflammatory mediator and a driver of chronic inflammation due to its ability to act as a carrier of extracellular DNA,[22] and as an antimicrobial molecule through its capacity to form pores in bacterial membranes. These properties suggest that IL-26 can be categorized as a kinocidin.
IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death. IL-26 is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore,
Concerning host defense to viruses, the role of IL-26 appears to be related to the expression of IL-26R by epithelial cells as these constitute the first barrier against many viruses. Elevated serum levels of IL-26 were detected in patients with chronic infection by hepatitis C virus. Moreover, the sensitivity of NK cells to IL-26 might trigger the ability to kill the virus-infected host cells.[23]
So far, the role of IL-26 in acute inflammation has not been properly studied, and most biological functions of IL-26 have been identified in pathological situations that feature chronic inflammation. The expression of IL-26 is elevated in the inflamed colonic mucosa of patients with
A novel effect of IL-26 produced by donor-derived CD26+ CD4+ T cells on the pathophysiology of pulmonary chronic GVHD was observed in a murine model.[15]
The roles of IL-26 in normal physiology remain unknown. By contrast to other IL-10 cytokine family members, no induction of primary human keratinocyte proliferation in response to IL-26 has been detected.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000111536 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: interleukin 26".
- ^ PMID 10729163.
- S2CID 11291286.
- ^ PMID 30809226.
- ^ PMID 14764663.
- ^ PMID 15178681.
- PMID 16005068.
- PMID 20947410.
- S2CID 25613652.
- ^ S2CID 3186117.
- PMID 18490742.
- ^ PMID 23055831.
- ^ PMID 25786689.
- ^ PMID 12023331.
- ^ PMID 25157980.
- PMID 25291379.
- PMID 18978771.
- S2CID 46419911.
- PMID 15120644.
- ^ PMID 26168081.
- S2CID 8052342.
- S2CID 3932106.
- PMID 22236965.
- S2CID 11325105.
Further reading
- Davila S, Froeling FE, Tan A, Bonnard C, Boland GJ, Snippe H, et al. (April 2010). "New genetic associations detected in a host response study to hepatitis B vaccine". Genes and Immunity. 11 (3): 232–8. S2CID 11183658.
- Silverberg MS, Cho JH, Rioux JD, McGovern DP, Wu J, Annese V, et al. (February 2009). "Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study". Nature Genetics. 41 (2): 216–20. PMID 19122664.
- Dambacher J, Beigel F, Zitzmann K, De Toni EN, Göke B, Diepolder HM, et al. (September 2009). "The role of the novel Th17 cytokine IL-26 in intestinal inflammation". Gut. 58 (9): 1207–17. S2CID 3186117.
- Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Molecular Medicine. 16 (7–8): 247–53. PMID 20379614.
- Sheikh F, Baurin VV, Lewis-Antes A, Shah NK, Smirnov SV, Anantha S, et al. (February 2004). "Cutting edge: IL-26 signals through a novel receptor complex composed of IL-20 receptor 1 and IL-10 receptor 2". Journal of Immunology. 172 (4): 2006–10. PMID 14764663.
- Siezen CL, Bont L, Hodemaekers HM, Ermers MJ, Doornbos G, Van't Slot R, et al. (April 2009). "Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes". The Pediatric Infectious Disease Journal. 28 (4): 333–5. S2CID 25601837.
- Vandenbroeck K, Cunningham S, Goris A, Alloza I, Heggarty S, Graham C, et al. (October 2003). "Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis". Arthritis and Rheumatism. 48 (10): 2773–8. PMID 14558082.
- Dumoutier L, Van Roost E, Ameye G, Michaux L, Renauld JC (December 2000). "IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes". Genes and Immunity. 1 (8): 488–94. S2CID 1477389.
- Kantarci OH, Hebrink DD, Schaefer-Klein J, Sun Y, Achenbach S, Atkinson EJ, et al. (March 2008). "Interferon gamma allelic variants: sex-biased multiple sclerosis susceptibility and gene expression". Archives of Neurology. 65 (3): 349–57. PMID 18332247.
- Janssen R, Bont L, Siezen CL, Hodemaekers HM, Ermers MJ, Doornbos G, et al. (September 2007). "Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes". The Journal of Infectious Diseases. 196 (6): 826–34. PMID 17703412.
- Wang K, Baldassano R, Zhang H, Qu HQ, Imielinski M, Kugathasan S, et al. (May 2010). "Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects". Human Molecular Genetics. 19 (10): 2059–67. PMID 20176734.
- Schuurhof A, Bont L, Siezen CL, Hodemaekers H, van Houwelingen HC, Kimman TG, et al. (June 2010). "Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls". Pediatric Pulmonology. 45 (6): 608–13. S2CID 24678182.