Interleukin 15-like

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Interleukin 15-like (IL-15L) is an interleukin, a type of cytokine signaling in the immune system. It is a secreted protein of approximately 120 amino acids [1] and related to IL-2 and IL-15.

Intact IL-15L genes are found in bony fish, [2] [3] cartilaginous fish, [4] [5] reptiles, and many mammals. [6] However, in humans and mice only an IL-15L pseudogene is found. [6] The location of the IL-15L gene in the genome is conserved from sharks to mammals and on a different chromosome than IL-2 and IL-15. [2] [3] [5] [6]

Bony fish (trout) IL-15L specifically stimulates the expression of type 2 immunity cytokines IL-4/13A and IL-4/13B (homologs of IL-4 and IL-13. [7] [8] ), probably by stimulating ILC2 cells; [1] this is quite different from the functions found for IL-2 [9] [10] and IL-15, [9] [11] including in fish. [1] [12] [13] For mammalian IL-15L, a function has not been found yet. In both fish and mammals, IL-15L seems to be quite dependent for its stability on “heterodimer” formation with IL-15Rα, [1] [6] and functions for fish IL-15L could only be found if partnered with (presented “in trans” by) IL-15Rα [1]

It is unclear why many mammals, and also birds and amphibians, [6] lost IL-15L. It has been postulated that in fish the IL-15L cytokine resides at the beginning of a type 2 immune cascade, [1] a function that in mammals is performed by cytokines such as TSLP, IL-25, and IL-33; none of these three cytokines have been found in fish, [14] and their evolution in tetrapod species may have made IL-15L redundant.

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<span class="mw-page-title-main">Interleukin 10</span> Anti-inflammatory cytokine

Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans, interleukin 10 is encoded by the IL10 gene. IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively.

<span class="mw-page-title-main">Interleukin 2</span> Mammalian protein found in Homo sapiens

Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15.5–16 kDa protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's natural response to microbial infection, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes. The major sources of IL-2 are activated CD4+ T cells and activated CD8+ T cells.

<span class="mw-page-title-main">Interleukin 4</span> Mammalian protein found in Mus musculus

The interleukin 4 is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Th2 cells, eosinophils and basophils. It is closely related and has functions similar to IL-13.

<span class="mw-page-title-main">Interleukin 13</span> Protein and coding gene in humans

Interleukin 13 (IL-13) is a protein that in humans is encoded by the IL13 gene. IL-13 was first cloned in 1993 and is located on chromosome 5q31.1 with a length of 1.4kb. It has a mass of 13 kDa and folds into 4 alpha helical bundles. The secondary structural features of IL-13 are similar to that of Interleukin 4 (IL-4); however it only has 25% sequence identity to IL-4 and is capable of IL-4 independent signaling. IL-13 is a cytokine secreted by T helper type 2 (Th2) cells, CD4 cells, natural killer T cell, mast cells, basophils, eosinophils and nuocytes. Interleukin-13 is a central regulator in IgE synthesis, goblet cell hyperplasia, mucus hypersecretion, airway hyperresponsiveness, fibrosis and chitinase up-regulation. It is a mediator of allergic inflammation and different diseases including asthma.

<span class="mw-page-title-main">IL-2 receptor</span> Lymphocyte receptor specific for Interleukin-2

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<span class="mw-page-title-main">Interleukin 23 subunit alpha</span>

Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. IL-23 is produced by dendritic cells and macrophages.

<span class="mw-page-title-main">Interleukin 15</span> Cytokine with structural similarity to Interleukin-2

Interleukin-15 (IL-15) is a protein that in humans is encoded by the IL15 gene. IL-15 is an inflammatory cytokine with structural similarity to Interleukin-2 (IL-2). Like IL-2, IL-15 binds to and signals through a complex composed of IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain. IL-15 is secreted by mononuclear phagocytes following infection by virus(es). This cytokine induces the proliferation of natural killer cells, i.e. cells of the innate immune system whose principal role is to kill virally infected cells.

<span class="mw-page-title-main">Interleukin 18</span>

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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.

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">IL13RA2</span> Protein-coding gene in the species Homo sapiens

Interleukin-13 receptor subunit alpha-2 (IL-13Rα2), also known as CD213A2, is a membrane bound protein that in humans is encoded by the IL13RA2 gene.

<span class="mw-page-title-main">Interleukin 37</span> Protein-coding gene in the species Homo sapiens

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Interleukin-10 receptor (IL-10R) is a type II cytokine receptor. The receptor is tetrameric, composed of 2α and 2β subunits. The α subunit is expressed on haematopoietic cells whilst the β subunit is expressed ubiquitously. The α subunit is exclusive to interleukin-10, however the β subunit is shared with other type II cytokine receptors such as IL-22R, IL-26R and INFλR.

<span class="mw-page-title-main">IL2RA</span> Mammalian protein found in Homo sapiens

Interleukin-2 receptor alpha chain is a protein involved in assembly of high-affinity Interleukin-2 receptor, consisting of alpha (IL2RA), beta (IL2RB) and the common gamma chain (IL2RG). As the name indicates, this receptor interacts with pleiotropic cytokine called Interleukin-2, which effect is mainly important for immune homeostasis.

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

Interleukin-17 receptor (IL-17R) is a cytokine receptor which belongs to new subfamily of receptors binding proinflammatory cytokine interleukin 17A, a member of IL-17 family ligands produced by T helper 17 cells (Th17). IL-17R family consists of 5 members: IL-17RA, IL-17RB, IL-17RC, IL-17RD and IL-17RE. Functional IL-17R is a transmembrane receptor complex usually consisting of one IL-17RA, which is a founding member of the family, and second other family subunit, thus forming heteromeric receptor binding different ligands. IL-17A, a founding member of IL-17 ligand family binds to heteromeric IL-17RA/RC receptor complex. IL-17RB binds preferentially IL-17B and IL-17E and heteromeric IL-17RA/RE complex binds IL-17C. However, there is still unknown ligand for IL-17RD. The first identified member IL-17RA is located on human chromosome 22, whereas other subunits IL-17RB to IL-17RD are encoded within human chromosome 3.

<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.

The IL10 family is a family of interleukins.

B10 cells are a sub-class of Regulatory B-cell that are involved in inhibiting immune responses in both humans and mice. B10 cells are named for their ability to produce inhibitory interleukin: Interleukin-10 (IL-10). One of their unique abilities is that they suppress the innate and adaptive immune signals, making them important for regulating the inflammatory response. Like the B-cell, the B10 cell requires antigen specific binding to the surface of CD5 receptor to illicit a response from the T-cell. Once an antigen binds to the CD19 receptor, immediate downregulation in B-cell antigen receptor (BCR) signal expression occurs and mediates the release of IL-10 cytokines.

References

  1. 1 2 3 4 5 6 Yamaguchi, Takuya; Chang, Chia Jung; Karger, Axel; Keller, Markus; Pfaff, Florian; Wangkahart, Eakapol; Wang, Tiehui; Secombes, Christopher J.; Kimoto, Azusa; Furihata, Mitsuru; Hashimoto, Keiichiro; Fischer, Uwe; Dijkstra, Johannes M. (2020). "Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response". Frontiers in Immunology. 11: 549319. doi: 10.3389/fimmu.2020.549319 . ISSN   1664-3224. PMC   7658486 . PMID   33193315.
  2. 1 2 Gunimaladevi, I.; Savan, Ram; Sato, Kenji; Yamaguchi, Ryoji; Sakai, Masahiro (April 2007). "Characterization of an interleukin-15 like (IL-15L) gene from zebrafish (Danio rerio)". Fish & Shellfish Immunology. 22 (4): 351–362. doi:10.1016/j.fsi.2006.05.009. PMID   16919968.
  3. 1 2 Fang, Wei; Xiang, Li-Xin; Shao, Jian-Zhong; Wen, Yi; Chen, Shu-Yun (March 2006). "Identification and characterization of an interleukin-15 homologue from Tetraodon nigroviridis". Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. 143 (3): 335–343. doi:10.1016/j.cbpb.2005.12.009. PMID   16455279.
  4. ↑ Dijkstra, Johannes M. (2014-07-10). "TH2 and Treg candidate genes in elephant shark". Nature. 511 (7508): E7–E9. Bibcode:2014Natur.511E...7D. doi:10.1038/nature13446. ISSN   0028-0836. PMID   25008534. S2CID   4447611.
  5. 1 2 Dijkstra, Johannes M. (February 2021). "A method for making alignments of related protein sequences that share very little similarity; shark interleukin 2 as an example". Immunogenetics. 73 (1): 35–51. doi:10.1007/s00251-020-01191-5. ISSN   0093-7711. PMID   33512550. S2CID   231770873.
  6. 1 2 3 4 5 Dijkstra, Johannes M.; Takizawa, Fumio; Fischer, Uwe; Friedrich, Maik; Soto-Lampe, Veronica; Lefèvre, Christophe; Lenk, Matthias; Karger, Axel; Matsui, Taei; Hashimoto, Keiichiro (February 2014). "Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα". Immunogenetics. 66 (2): 93–103. doi:10.1007/s00251-013-0747-0. ISSN   0093-7711. PMC   3894449 . PMID   24276591.
  7. ↑ Li, Jia-Hui; Shao, Jian-Zhong; Xiang, Li-Xin; Wen, Yi (March 2007). "Cloning, characterization and expression analysis of pufferfish interleukin-4 cDNA: The first evidence of Th2-type cytokine in fish". Molecular Immunology. 44 (8): 2078–2086. doi:10.1016/j.molimm.2006.09.010. PMID   17084456.
  8. ↑ Ohtani, Maki; Hayashi, Nobuhiro; Hashimoto, Keiichiro; Nakanishi, Teruyuki; Dijkstra, Johannes Martinus (July 2008). "Comprehensive clarification of two paralogous interleukin 4/13 loci in teleost fish". Immunogenetics. 60 (7): 383–397. doi:10.1007/s00251-008-0299-x. ISSN   0093-7711. PMID   18560827. S2CID   24675205.
  9. 1 2 Waldmann, Thomas A. (August 2006). "The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design". Nature Reviews Immunology. 6 (8): 595–601. doi:10.1038/nri1901. ISSN   1474-1733. PMID   16868550. S2CID   33995454.
  10. ↑ Malek, Thomas R. (2008-04-01). "The Biology of Interleukin-2". Annual Review of Immunology. 26 (1): 453–479. doi:10.1146/annurev.immunol.26.021607.090357. ISSN   0732-0582. PMID   18062768.
  11. ↑ Waldmann, Thomas A. (December 2013). "The Biology of IL-15: Implications for Cancer Therapy and the Treatment of Autoimmune Disorders". Journal of Investigative Dermatology Symposium Proceedings. 16 (1): S28–S30. doi: 10.1038/jidsymp.2013.8 . PMID   24326545.
  12. ↑ Wang, Tiehui; Holland, Jason W.; Carrington, Allison; Zou, Jun; Secombes, Christopher J. (2007-08-01). "Molecular and Functional Characterization of IL-15 in Rainbow Trout Oncorhynchus mykiss: A Potent Inducer of IFN-γ Expression in Spleen Leukocytes". The Journal of Immunology. 179 (3): 1475–1488. doi: 10.4049/jimmunol.179.3.1475 . ISSN   0022-1767. PMID   17641013. S2CID   45106342.
  13. ↑ Wang, Tiehui; Hu, Yehfang; Wangkahart, Eakapol; Liu, Fuguo; Wang, Alex; Zahran, Eman; Maisey, Kevin R.; Liu, Min; Xu, Qiaoqing; Imarai, Mónica; Secombes, Christopher J. (2018-07-26). "Interleukin (IL)-2 Is a Key Regulator of T Helper 1 and T Helper 2 Cytokine Expression in Fish: Functional Characterization of Two Divergent IL2 Paralogs in Salmonids". Frontiers in Immunology. 9: 1683. doi: 10.3389/fimmu.2018.01683 . ISSN   1664-3224. PMC   6070626 . PMID   30093902.
  14. ↑ Yamaguchi, Takuya; Takizawa, Fumio; Fischer, Uwe; Dijkstra, Johannes (2015-11-17). "Along the Axis between Type 1 and Type 2 Immunity; Principles Conserved in Evolution from Fish to Mammals". Biology. 4 (4): 814–859. doi: 10.3390/biology4040814 . ISSN   2079-7737. PMC   4690019 . PMID   26593954.
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