IL-15 regulates immune responses through:
NK and T Cell Activation: Enhances NK cell cytotoxicity and CD8+ T cell proliferation .
Anti-Apoptotic Effects: Upregulates Bcl-xL via STAT6 signaling, preventing lymphocyte apoptosis .
Inflammation Modulation: Drives pro-inflammatory cytokine production (e.g., IFN-γ) .
IL-15 mutant (IL15Δ/Δ) rats exhibit:
Absence of uterine NK cells, leading to hyper-invasive trophoblasts and placental abnormalities .
Altered gene expression in implantation sites, including downregulation of immune-related genes (Gzmc, Prf1, Ccl5) and upregulation of neurodevelopmental genes (Gria4, Crym) .
Sepsis Treatment: Recombinant IL-15 (0.5–1.5 μg doses) increased T/NK cell counts and IFN-γ levels, improving survival in septic rats .
Inflammatory Disease Targeting:
IL-15 dysregulation in rats is linked to:
Autoimmune Disorders: Rheumatoid arthritis, psoriasis, and celiac disease .
Infectious Diseases: Enhanced susceptibility to Listeria and periodontal pathogens .
Reproductive Abnormalities: Placental defects due to NK cell deficiency .
Interleukin-15 (IL-15) is a cytokine that plays a crucial role in the immune system by promoting the proliferation and maintenance of natural killer (NK) cells and CD8+ T cells. It is structurally and functionally related to Interleukin-2 (IL-2) and is involved in various immunological responses. Recombinant IL-15, including that derived from rats, is used in research to study its effects and potential therapeutic applications.
IL-15 was discovered in 1994 as a cytokine that induces the proliferation of T cells independently of IL-2. It shares common receptor chains with IL-2, specifically the IL-2/15Rβ (CD122) and γc (CD132) chains. The specificity of IL-15 is conferred by its unique alpha receptor chain, IL-15Rα (CD215), which has a high affinity for IL-15 independently of the β and γc chains .
IL-15 is a pleiotropic cytokine, meaning it has multiple effects on different cell types. It is essential for the development, survival, and function of NK cells, NKT cells, γδ T lymphocytes, and memory CD8+ T cells. IL-15 is involved in both innate and adaptive immunity, making it a critical component of the immune response .
IL-15 exerts its effects through a complex signaling pathway. It binds to the IL-15Rα chain, which presents IL-15 in trans to cells expressing the IL-2/15Rβ and γc chains. This trans-presentation mechanism is unique to IL-15 and allows it to efficiently stimulate target cells. The binding of IL-15 to its receptor activates several downstream signaling pathways, including the JAK/STAT, PI3K/Akt, and MAPK pathways, leading to the proliferation and activation of immune cells .
Due to its ability to stimulate the immune system, IL-15 has been investigated for its potential therapeutic applications, particularly in cancer immunotherapy. IL-15 can enhance the cytotoxic activity of NK cells and CD8+ T cells, making it a promising candidate for boosting anti-tumor immunity. However, the clinical use of IL-15 has been limited by its short half-life and the need for sustained exposure to achieve optimal therapeutic effects .
Recombinant IL-15, including rat-derived IL-15, is produced using genetic engineering techniques. It is used in research to study the biological functions and therapeutic potential of IL-15. Recombinant IL-15 can be administered in various forms, including as a single agent or in combination with other immunotherapeutic agents. Recent studies have focused on developing long-acting forms of IL-15 to overcome the limitations of its short half-life .