Interleukin-15 (IL-15) is a cytokine, a type of signaling molecule that plays a crucial role in the immune system. It belongs to the interleukin-2 (IL-2) cytokine family and shares some biological activities with IL-2. IL-15 is involved in the regulation and activation of various immune cells, particularly T cells and natural killer (NK) cells.
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IL-15 plays an important role in innate and adaptive immunity. It is a T cell proliferation factor that shares IL-2 receptor β subunit with IL-2. IL-15 is a pleiotropic cytokine, constitutively expressed by many types of cells such as macrophages, monocytes, dendritic cells (DCs), T cells, as well as epithelial cells, fibroblasts, keratinocytes, and nerve cells. However, IL-15 is mainly produced by macrophages, monocytes, and DCs.
IL-15 is especially involved in lymphocyte and NK cell functioning and homeostasis. IL-15 signals through a heterotrimeric receptor which consists of three subunits, the IL-15 receptor α (IL-15Rα or CD215) specific subunit, IL2/IL-15 receptor β subunit (IL2/IL-15Rβ), and γ (CD132) subunit, a common chain for other cytokines such as IL-2, IL-4, IL-7, IL-9, and IL-21. IL-15 signaling requires Janus kinases (Jak)-1 and Jak-3.
IL-15 acts on many cells of the immune system, being able to increase the proliferation of B cells and secretion of immunoglobulins and is critical for the ontogeny of NK and CD8+ T cells, inducing cell activation, proliferation, cytolytic activity, and the production of cytokines such as interferon-γ (IFN-γ) by these cells. Although IL-2 and IL-15 present similar functions in lymphocytes, there are some differences. IL-15 does not exert significant effects on regulatory T cells (Tregs), a subset of cells that inhibit antitumor immunity and promote tumor development and progression; and by acting as a survival factor of CD8 memory T cells, it plays an important role in supporting the long-term maintenance, high-avidity T cell responses to malignant cells.
Unfortunately, IL-15 exhibits a dark side. This cytokine also presents pro-inflammatory potential, being involved in the pathogenesis of several autoimmune diseases. IL-15 induces the production of pro-inflammatory cytokines, such as IL-1β and tumor-necrosis factor-α (TNFα), and promotes the survival of a self-directed memory T cell subpopulation. IL-15 has been detected in patients with such autoimmune diseases as inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis (MS). In these patients, both elevated level of IL-15 in body fluids and disordered IL-15 expression has been noted when compared with healthy controls.
Interleukin-15 (IL-15) has been studied as a potential biomarker in various clinical contexts, particularly in the field of immunology and inflammatory diseases. A biomarker is a measurable substance or characteristic that can be used as an indicator of normal biological processes, pathogenic processes, or responses to therapeutic interventions.
- Inflammatory and Autoimmune Diseases: Elevated levels of IL-15 have been observed in patients with various inflammatory and autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Monitoring IL-15 levels may provide insights into the degree of inflammation and immune activation in these conditions.
- Cancer: IL-15 has been implicated in antitumor immune responses, and its levels may be altered in cancer patients. Researchers are exploring the use of IL-15 as a biomarker to assess the immune status of cancer patients and to predict responses to immunotherapy.
- Infectious Diseases: IL-15 is involved in the immune response to infections. Changes in IL-15 levels may be indicative of ongoing infections or immune system activation. Monitoring IL-15 levels could be relevant in infectious diseases, including viral infections.
- Monitoring Immune System Activation: IL-15 plays a key role in activating and proliferating T cells and natural killer (NK) cells. As such, measuring IL-15 levels can provide information about the overall activation status of the immune system.
- Therapeutic Monitoring: In the context of immunotherapy, such as treatments that involve the administration of IL-15 or IL-15 superagonists, monitoring IL-15 levels may be important for assessing treatment response and managing potential side effects.
It's important to note that while IL-15 shows promise as a biomarker, its utility in clinical practice may vary depending on the specific disease or condition. Measuring biomarkers often requires careful consideration of factors that could influence results, such as the patient's age, sex, and other comorbidities.
