TY - JOUR
T1 - Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response
AU - Yamaguchi, Takuya
AU - Chang, Chia Jung
AU - Karger, Axel
AU - Keller, Markus
AU - Pfaff, Florian
AU - Wangkahart, Eakapol
AU - Wang, Tiehui
AU - Secombes, Christopher J.
AU - Kimoto, Azusa
AU - Furihata, Mitsuru
AU - Hashimoto, Keiichiro
AU - Fischer, Uwe
AU - Dijkstra, Johannes M.
N1 - Publisher Copyright:
© Copyright © 2020 Yamaguchi, Chang, Karger, Keller, Pfaff, Wangkahart, Wang, Secombes, Kimoto, Furihata, Hashimoto, Fischer and Dijkstra.
PY - 2020/10/29
Y1 - 2020/10/29
N2 - Related interleukin-2, -15, and -15-like (IL-2, -15, and -15L) are ancient cytokines, with all three genes surviving in extant fish and some mammals. The present study is the first to identify IL-15L functions, namely in rainbow trout. In isolated trout splenocytes, and in vivo, purified recombinant IL-15L+IL-15Rα molecules induced expression of IL-4 and IL-13 homologs, which are markers of type 2 immunity. In contrast, trout IL-15 stimulated type 1 immunity markers, thus IL-15 and IL-15L can have opposing functions. Trout IL-15L was more dependent on “in trans” presentation by the receptor chain IL-15Rα than IL-15, and stimulated CD4−CD8−(IgM−) lymphocytes from thymus and spleen. We propose an important role for IL-15L early in the type 2 immunity cytokine cascade. Trout IL-2 and IL-15 exhibited features reminiscent of their mechanistic and functional dichotomy observed in mammals; for example, IL-15 but not IL-2 required a receptor alpha chain (only IL-15Rα in the case of fish) for its stability, and only IL-15 was efficient in stimulating lymphocytes from mucosal tissues. Data suggest that IL-15L and IL-15 may be particularly effective in stimulating innate lymphocyte type 2 cells (ILC2) and natural killer (NK) cells, respectively, but further identification of the cell types is needed. An interesting finding different from in mammals was the efficient stimulation of CD4+CD8+ thymocytes by IL-2. In short, this study presents fundamental information on the evolution of the IL-2/15/15L cytokine family.
AB - Related interleukin-2, -15, and -15-like (IL-2, -15, and -15L) are ancient cytokines, with all three genes surviving in extant fish and some mammals. The present study is the first to identify IL-15L functions, namely in rainbow trout. In isolated trout splenocytes, and in vivo, purified recombinant IL-15L+IL-15Rα molecules induced expression of IL-4 and IL-13 homologs, which are markers of type 2 immunity. In contrast, trout IL-15 stimulated type 1 immunity markers, thus IL-15 and IL-15L can have opposing functions. Trout IL-15L was more dependent on “in trans” presentation by the receptor chain IL-15Rα than IL-15, and stimulated CD4−CD8−(IgM−) lymphocytes from thymus and spleen. We propose an important role for IL-15L early in the type 2 immunity cytokine cascade. Trout IL-2 and IL-15 exhibited features reminiscent of their mechanistic and functional dichotomy observed in mammals; for example, IL-15 but not IL-2 required a receptor alpha chain (only IL-15Rα in the case of fish) for its stability, and only IL-15 was efficient in stimulating lymphocytes from mucosal tissues. Data suggest that IL-15L and IL-15 may be particularly effective in stimulating innate lymphocyte type 2 cells (ILC2) and natural killer (NK) cells, respectively, but further identification of the cell types is needed. An interesting finding different from in mammals was the efficient stimulation of CD4+CD8+ thymocytes by IL-2. In short, this study presents fundamental information on the evolution of the IL-2/15/15L cytokine family.
KW - IL-15
KW - IL-15-like
KW - IL-15Rα
KW - IL-2
KW - evolution
KW - fish
KW - type 2 immunity
UR - http://www.scopus.com/inward/record.url?scp=85096022299&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.549319
DO - 10.3389/fimmu.2020.549319
M3 - Article
C2 - 33193315
AN - SCOPUS:85096022299
SN - 1664-3224
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 549319
ER -