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 - Acknowledgments
We thank Mrs. Susann Schares and Katrin Giesow for excellent technical assistance and Dr. Gunther Keil for his valuable advice regarding expression of recombinant proteins in insect cells. We also thank Prof. Oriol Sunyer from the University of Pennsylvania, USA, for providing us mAbs against rainbow trout CD4. A large part of this manuscript has been released as a pre-print (116).
Funding
TY and UF were supported by the EU FP7 Grant 311993 (TARGETFISH) and the German Research Council Grant No. FI 604/7-1. JD was supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan, Grants-in-Aid for Scientific Research No. 25450319. TW received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland), that was funded by the Scottish Funding Council (grant reference HR09011). EW was supported by the Ministry of Science and Technology of Thailand and Mahasarakham University.
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 - evolution
KW - fish
KW - IL-15
KW - IL-15-like
KW - IL-15Rα
KW - IL-2
KW - type 2 immunity
UR - http://www.scopus.com/inward/record.url?scp=85096022299&partnerID=8YFLogxK
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2020.549319/full#supplementary-material
U2 - 10.3389/fimmu.2020.549319
DO - 10.3389/fimmu.2020.549319
M3 - Article
C2 - 33193315
AN - SCOPUS:85096022299
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 549319
ER -