Interleukin 15-like

{{Short description|Cytokine}}

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{{Cite journal |last1=Yamaguchi |first1=Takuya |last2=Chang |first2=Chia Jung |last3=Karger |first3=Axel |last4=Keller |first4=Markus |last5=Pfaff |first5=Florian |last6=Wangkahart |first6=Eakapol |last7=Wang |first7=Tiehui |last8=Secombes |first8=Christopher J. |last9=Kimoto |first9=Azusa |last10=Furihata |first10=Mitsuru |last11=Hashimoto |first11=Keiichiro |last12=Fischer |first12=Uwe |last13=Dijkstra |first13=Johannes M. |date=2020 |title=Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response |journal=Frontiers in Immunology |volume=11 |pages=549319 |doi=10.3389/fimmu.2020.549319 |issn=1664-3224 |pmc=7658486 |pmid=33193315|doi-access=free }} and related to IL-2 and IL-15.

Intact IL-15L genes are found in bony fish,{{Cite journal |last1=Gunimaladevi |first1=I. |last2=Savan |first2=Ram |last3=Sato |first3=Kenji |last4=Yamaguchi |first4=Ryoji |last5=Sakai |first5=Masahiro |date=April 2007 |title=Characterization of an interleukin-15 like (IL-15L) gene from zebrafish (Danio rerio) |url=https://linkinghub.elsevier.com/retrieve/pii/S1050464806001136 |journal=Fish & Shellfish Immunology |language=en |volume=22 |issue=4 |pages=351–362 |doi=10.1016/j.fsi.2006.05.009|pmid=16919968 |url-access=subscription }}{{Cite journal |last1=Fang |first1=Wei |last2=Xiang |first2=Li-Xin |last3=Shao |first3=Jian-Zhong |last4=Wen |first4=Yi |last5=Chen |first5=Shu-Yun |date=March 2006 |title=Identification and characterization of an interleukin-15 homologue from Tetraodon nigroviridis |url=https://linkinghub.elsevier.com/retrieve/pii/S1096495905003064 |journal=Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology |language=en |volume=143 |issue=3 |pages=335–343 |doi=10.1016/j.cbpb.2005.12.009|pmid=16455279 |url-access=subscription }} cartilaginous fish,{{Cite journal |last=Dijkstra |first=Johannes M. |date=2014-07-10 |title=TH2 and Treg candidate genes in elephant shark |url=http://www.nature.com/articles/nature13446 |journal=Nature |language=en |volume=511 |issue=7508 |pages=E7–E9 |doi=10.1038/nature13446 |pmid=25008534 |bibcode=2014Natur.511E...7D |s2cid=4447611 |issn=0028-0836|url-access=subscription }}{{Cite journal |last=Dijkstra |first=Johannes M. |date=February 2021 |title=A method for making alignments of related protein sequences that share very little similarity; shark interleukin 2 as an example |url=http://link.springer.com/10.1007/s00251-020-01191-5 |journal=Immunogenetics |language=en |volume=73 |issue=1 |pages=35–51 |doi=10.1007/s00251-020-01191-5 |pmid=33512550 |s2cid=231770873 |issn=0093-7711|url-access=subscription }} reptiles, and many mammals.{{Cite journal |last1=Dijkstra |first1=Johannes M. |last2=Takizawa |first2=Fumio |last3=Fischer |first3=Uwe |last4=Friedrich |first4=Maik |last5=Soto-Lampe |first5=Veronica |last6=Lefèvre |first6=Christophe |last7=Lenk |first7=Matthias |last8=Karger |first8=Axel |last9=Matsui |first9=Taei |last10=Hashimoto |first10=Keiichiro |date=February 2014 |title=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 |journal=Immunogenetics |language=en |volume=66 |issue=2 |pages=93–103 |doi=10.1007/s00251-013-0747-0 |issn=0093-7711 |pmc=3894449 |pmid=24276591}} However, in humans and mice only an IL-15L pseudogene is found. 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.

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.{{Cite journal |last1=Li |first1=Jia-Hui |last2=Shao |first2=Jian-Zhong |last3=Xiang |first3=Li-Xin |last4=Wen |first4=Yi |date=March 2007 |title=Cloning, characterization and expression analysis of pufferfish interleukin-4 cDNA: The first evidence of Th2-type cytokine in fish |url=https://linkinghub.elsevier.com/retrieve/pii/S0161589006005918 |journal=Molecular Immunology |language=en |volume=44 |issue=8 |pages=2078–2086 |doi=10.1016/j.molimm.2006.09.010|pmid=17084456 |url-access=subscription }}{{Cite journal |last1=Ohtani |first1=Maki |last2=Hayashi |first2=Nobuhiro |last3=Hashimoto |first3=Keiichiro |last4=Nakanishi |first4=Teruyuki |last5=Dijkstra |first5=Johannes Martinus |date=July 2008 |title=Comprehensive clarification of two paralogous interleukin 4/13 loci in teleost fish |url=http://link.springer.com/10.1007/s00251-008-0299-x |journal=Immunogenetics |language=en |volume=60 |issue=7 |pages=383–397 |doi=10.1007/s00251-008-0299-x |pmid=18560827 |s2cid=24675205 |issn=0093-7711|url-access=subscription }}), probably by stimulating ILC2 cells; this is quite different from the functions found for IL-2{{Cite journal |last=Waldmann |first=Thomas A. |date=August 2006 |title=The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design |url=http://www.nature.com/articles/nri1901 |journal=Nature Reviews Immunology |language=en |volume=6 |issue=8 |pages=595–601 |doi=10.1038/nri1901 |pmid=16868550 |s2cid=33995454 |issn=1474-1733|url-access=subscription }}{{Cite journal |last=Malek |first=Thomas R. |date=2008-04-01 |title=The Biology of Interleukin-2 |url=https://www.annualreviews.org/doi/10.1146/annurev.immunol.26.021607.090357 |journal=Annual Review of Immunology |language=en |volume=26 |issue=1 |pages=453–479 |doi=10.1146/annurev.immunol.26.021607.090357 |pmid=18062768 |issn=0732-0582|url-access=subscription }} and IL-15,{{Cite journal |last=Waldmann |first=Thomas A. |date=December 2013 |title=The Biology of IL-15: Implications for Cancer Therapy and the Treatment of Autoimmune Disorders |journal=Journal of Investigative Dermatology Symposium Proceedings |language=en |volume=16 |issue=1 |pages=S28–S30 |doi=10.1038/jidsymp.2013.8|pmid=24326545 |doi-access=free }} including in fish.{{Cite journal |last1=Wang |first1=Tiehui |last2=Holland |first2=Jason W. |last3=Carrington |first3=Allison |last4=Zou |first4=Jun |last5=Secombes |first5=Christopher J. |date=2007-08-01 |title=Molecular and Functional Characterization of IL-15 in Rainbow Trout Oncorhynchus mykiss: A Potent Inducer of IFN-γ Expression in Spleen Leukocytes |journal=The Journal of Immunology |language=en |volume=179 |issue=3 |pages=1475–1488 |doi=10.4049/jimmunol.179.3.1475 |pmid=17641013 |s2cid=45106342 |issn=0022-1767|doi-access=free }}{{Cite journal |last1=Wang |first1=Tiehui |last2=Hu |first2=Yehfang |last3=Wangkahart |first3=Eakapol |last4=Liu |first4=Fuguo |last5=Wang |first5=Alex |last6=Zahran |first6=Eman |last7=Maisey |first7=Kevin R. |last8=Liu |first8=Min |last9=Xu |first9=Qiaoqing |last10=Imarai |first10=Mónica |last11=Secombes |first11=Christopher J. |date=2018-07-26 |title=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 |journal=Frontiers in Immunology |volume=9 |pages=1683 |doi=10.3389/fimmu.2018.01683 |issn=1664-3224 |pmc=6070626 |pmid=30093902|doi-access=free }} 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, and functions for fish IL-15L could only be found if partnered with (presented “in trans” by) IL-15Rα

It is unclear why many mammals, and also birds and amphibians, lost IL-15L. It has been postulated that in fish the IL-15L cytokine resides at the beginning of a type 2 immune cascade, 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,{{Cite journal |last1=Yamaguchi |first1=Takuya |last2=Takizawa |first2=Fumio |last3=Fischer |first3=Uwe |last4=Dijkstra |first4=Johannes |date=2015-11-17 |title=Along the Axis between Type 1 and Type 2 Immunity; Principles Conserved in Evolution from Fish to Mammals |journal=Biology |language=en |volume=4 |issue=4 |pages=814–859 |doi=10.3390/biology4040814 |issn=2079-7737 |pmc=4690019 |pmid=26593954|doi-access=free }} and their evolution in tetrapod species may have made IL-15L redundant.