Interleukin 23 subunit alpha

Last updated
IL23A
Protein IL23A PDB 3D85.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IL23A , IL-23, IL-23A, IL23P19, P19, SGRF, Interleukin 23, interleukin 23 subunit alpha
External IDs OMIM: 605580 MGI: 1932410 HomoloGene: 12832 GeneCards: IL23A
Orthologs
SpeciesHumanMouse
Entrez

51561

83430

Ensembl

ENSG00000110944

ENSMUSG00000025383

UniProt

Q9NPF7

Q9EQ14

RefSeq (mRNA)

NM_016584

NM_031252

RefSeq (protein)

NP_057668

NP_112542

Location (UCSC) Chr 12: 56.33 – 56.34 Mb Chr 10: 128.13 – 128.13 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. [5] [6] The protein is also known as IL-23p19. It is one of the two subunits of the cytokine Interleukin-23.

Contents

Interleukin-23 (IL-23) is a heterodimeric cytokine composed of an Interleukin 23 alpha subunit and an IL-12p40 subunit. The IL-12p40, also known as Interleukin 12 subunit beta, is used by both IL-23 (where it partners with IL-23p19) and IL-12 (where it partners with IL-12A). [5] A functional receptor for IL-23 (the IL-23 receptor) has been identified and is composed of IL-12R β1 and IL-23R. [7]

Function

Produced by dendritic cells and macrophages, IL-23 is an important part of the inflammatory response against infection. It promotes upregulation of the matrix metalloprotease MMP9, increases angiogenesis and reduces CD8+ T-cell infiltration into tumours. IL-23 mediates its effects on both innate and adaptive arms of the immune system that express the IL-23 receptor. Th17 cells represent the most prominent T cell subset that responds to IL-23, although IL-23 has been implicated in inhibiting the development of regulatory T cell development in the intestine. Th17 cells produce IL-17, a proinflammatory cytokine that enhances T cell priming and stimulates the production of other proinflammatory molecules such as IL-1, IL-6, TNF-alpha, NOS-2, and chemokines resulting in inflammation.

The expression of IL23A is decreased after AHR knockdown in THP-1 cells and primary mouse macrophages. [8]

Clinical significance

Knockout mice deficient in either p40 or p19, or in either subunit of the IL-23 receptor (IL-23R and IL12R-β1) develop less severe symptoms of experimental autoimmune encephalomyelitis (EAE) and inflammatory bowel disease highlighting the importance of IL-23 in the inflammatory pathway. [9] [10]

Discovery

A computational search for IL-12 homologue genes found p19, a gene that encodes a cytokine chain. Experimental work revealed that p19 formed a heterodimer by binding to p40, a subunit of IL-12. This new heterodimer was named IL-23. [11]

Knockdown of AHR decreases the expression of IL23A in THP-1 cells and primary macrophage. [8]

See also

Related Research Articles

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<span class="mw-page-title-main">Interleukin 12</span> Interleukin

Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.

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<span class="mw-page-title-main">Interleukin 21</span> Mammalian protein found in humans

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<span class="mw-page-title-main">Interleukin 30</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Interleukin 26</span>

Interleukin-26 (IL-26) is a protein that in humans is encoded by the IL26 gene.

<span class="mw-page-title-main">Interleukin 25</span> Cytokine that belongs to the IL-17 cytokine family

Interleukin-25 (IL-25) – also known as interleukin-17E (IL-17E) – is a protein that in humans is encoded by the IL25 gene on chromosome 14. IL-25 was discovered in 2001 and is made up of 177 amino acids.

<span class="mw-page-title-main">Interleukin 22</span> Protein, encoded in humans by IL22 gene

Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.

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<span class="mw-page-title-main">Interleukin-12 subunit beta</span> Protein-coding gene in the species Homo sapiens

Subunit beta of interleukin 12 is a protein subunit that in humans is encoded by the IL12B gene. IL-12B is a common subunit of interleukin 12 and interleukin 23.

Interleukin 35 (IL-35) is a recently discovered anti-inflammatory cytokine from the IL-12 family. Member of IL-12 family - IL-35 is produced by wide range of regulatory lymphocytes and plays a role in immune suppression. IL-35 can block the development of Th1 and Th17 cells by limiting early T cell proliferation.

<span class="mw-page-title-main">Interleukin 12 receptor, beta 1 subunit</span> Protein and coding gene in humans

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<span class="mw-page-title-main">Interleukin-23 receptor</span> Protein-coding gene in the species Homo sapiens

The interleukin-23 receptor is a type I cytokine receptor. It is encoded in human by the IL23R gene. In complex with the interleukin-12 receptor β1 subunit (IL-12Rβ1), it is activated by the cytokine interleukin 23 (IL-23). The IL23R mRNA is 2.8 kilobases in length and includes 12 exons. The translated protein contains 629 amino acids; it is a type I penetrating protein and includes a signal peptide, an N-terminal fibronectin III-like domain and an intracellular part that contains three potential tyrosine phosphorylation domains. There are 24 IL23R splice variants in mitogen-activated lymphocytes. IL23R includes some single-nucleotide polymorphisms in the region encoding the domain that binds IL-23, which may lead to differences between people in Th17 activation. There is also a variant of IL-23R that consists of just the extracellular part and is known as soluble IL-23R. This form can compete with the membrane-bound form to bind IL-23, modulating the Th17 immune response and regulation of inflammation and immune function.

The interleukin-27 receptor is a type I cytokine receptor for interleukin-27. It is a heterodimer composed of the interleukin 27 receptor, alpha subunit and glycoprotein 130.

<span class="mw-page-title-main">IL17A</span> Protein-coding gene in the species Homo sapiens

Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene.

<span class="mw-page-title-main">Interleukin-17 receptor</span> Type of protein receptor

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<span class="mw-page-title-main">Interleukin-1 family</span> Group of cytokines playing a key role in the regulation of immune and inflammatory responses

The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.

<span class="mw-page-title-main">Interleukin 23</span> Heterodimeric cytokine acting as mediator of inflammation

Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 consists of a heterodimer between IL-12Rβ1 and IL-23R.

<span class="mw-page-title-main">Interleukin 17F</span>

Interleukin 17F (IL-17F) is signaling protein that is in human is encoded by the IL17F gene and is considered a pro-inflammatory cytokine. This protein belongs to the interleukin 17 family and is mainly produced by the T helper 17 cells after their stimulation with interleukin 23. However, IL-17F can be also produced by a wide range of cell types, including innate immune cells and epithelial cells.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000110944 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025383 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. (November 2000). "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12". Immunity. 13 (5): 715–25. doi: 10.1016/S1074-7613(00)00070-4 . PMID   11114383.
  6. ↑ "Entrez Gene: IL23A interleukin 23, alpha subunit p19".
  7. ↑ Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. (June 2002). "A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R". Journal of Immunology. 168 (11): 5699–708. doi: 10.4049/jimmunol.168.11.5699 . PMID   12023369.
  8. 1 2 Memari B, Bouttier M, Dimitrov V, Ouellette M, Behr MA, Fritz JH, White JH (November 2015). "Engagement of the Aryl Hydrocarbon Receptor in Mycobacterium tuberculosis-Infected Macrophages Has Pleiotropic Effects on Innate Immune Signaling". Journal of Immunology. 195 (9): 4479–91. doi: 10.4049/jimmunol.1501141 . PMID   26416282.
  9. ↑ Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M (July 2006). "IL-23 promotes tumour incidence and growth". Nature. 442 (7101): 461–5. Bibcode:2006Natur.442..461L. doi:10.1038/nature04808. PMID   16688182. S2CID   4431794.
  10. ↑ Kikly K, Liu L, Na S, Sedgwick JD (December 2006). "The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation". Current Opinion in Immunology. 18 (6): 670–5. doi:10.1016/j.coi.2006.09.008. PMID   17010592.
  11. ↑ Korn T, Bettelli E, Oukka M, Kuchroo VK (2009). "IL-17 and Th17 Cells". Annual Review of Immunology. 27: 485–517. doi:10.1146/annurev.immunol.021908.132710. PMID   19132915.

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