Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

Area of Science:

• Immunology
• Evolutionary Biology
• Comparative Genomics

Background:

• Interleukin-2 (IL-2), IL-15, and IL-15-like (IL-15L) are ancient cytokines conserved across vertebrates.
• Understanding their functions in diverse species like fish provides insights into immune system evolution.
• Previous research has not fully elucidated the specific roles of IL-15L.

Purpose of the Study:

• To characterize the functions of IL-15L in rainbow trout.
• To investigate the comparative roles of IL-15 and IL-15L in immune responses.
• To explore the evolutionary aspects of the IL-2/15/15L cytokine family.

Main Methods:

• Purified recombinant IL-15L and IL-15Rα molecules were used to stimulate isolated trout splenocytes and for in vivo studies.
• Gene expression analysis was performed to identify markers of type 1 and type 2 immunity (e.g., IL-4, IL-13 homologs).
• Flow cytometry was used to analyze lymphocyte populations stimulated by the cytokines.

Main Results:

• Trout IL-15L, particularly when presented by IL-15Rα, induced type 2 immunity markers (IL-4, IL-13 homologs).
• Trout IL-15 stimulated type 1 immunity markers, indicating opposing functions to IL-15L.
• IL-15L showed greater dependence on IL-15Rα for presentation compared to IL-15.
• Both cytokines stimulated distinct lymphocyte populations, with IL-2 showing unique effects on thymocytes in trout compared to mammals.

Conclusions:

• IL-15L plays a significant role early in the type 2 immunity cytokine cascade in fish.
• IL-15 and IL-15L exhibit functional dichotomy, similar to mammals, with distinct receptor dependencies and target cell preferences.
• The study provides fundamental insights into the evolution and conserved functions of the IL-2/15/15L cytokine family in vertebrates.