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.