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.

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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