IL15 (Interleukin-15) encodes a cytokine that is structurally related to IL-2 and shares many biological functions, but has distinct expression patterns and signaling mechanisms. IL-15 is critical for the development, survival, and function of natural killer (NK) cells, NK T cells, and certain T cell subsets. In the central nervous system, IL-15 is expressed in [neurons](/entities/neurons), [astrocytes](/entities/astrocytes), [microglia](/cell-types/microglia-neuroinflammation), and oligodendrocytes, where it plays important roles in neuroinflammation, synaptic plasticity, and neuroprotection[@polliz2002][@gomeznicola2014].
Gene Overview
Function
IL-15 is a cytokine with diverse functions in both immune and nervous systems:
Immune System
NK cell development and maintenance: IL-15 is essential for the survival, proliferation, and cytotoxic function of NK cells[@kennedy2000]
Memory CD8+ T cell homeostasis: IL-15 supports the maintenance of memory CD8+ T cells independent of antigen[@schluns2000]
NKT cell development: Critical for NKT cell development and function
Nervous System
Neuroprotection: IL-15 exhibits neuroprotective properties in models of Parkinson's disease and ALS through anti-apoptotic mechanisms[@panga2019]
Neuroinflammation: Modulates microglial activation and cytokine production
Synaptic plasticity: Involved in regulating synaptic transmission and plasticity in hippocampal neurons
Receptor Complex
IL-15 signals through a heterotrimeric receptor complex:
IL-15Rα (IL15RA): High-affinity binding subunit
IL-2Rβ (IL2RB): Shared with IL-2 receptor
Common γ chain (IL2RG): Signal transducing subunit
The IL-15/IL-15Rα complex can also present in trans to neighboring cells expressing IL-2Rβ/γc[@dubois2002].
Signaling Pathways
IL-15 activates multiple signaling cascades:
JAK/STAT pathway: Primarily JAK1/JAK3 and STAT3/STAT5
Alzheimer's Disease: IL-15 levels are elevated in AD brain tissue and cerebrospinal fluid; may contribute to neuroinflammation and [tau](/proteins/tau) pathology[@zhao2013]
Parkinson's Disease: Dysregulated IL-15 signaling implicated in dopaminergic neuron survival; IL-15 has shown neuroprotective effects in PD models[@ljunggren2015]
Amyotrophic Lateral Sclerosis (ALS): Elevated IL-15 in ALS patients and mouse models; dual role in both promoting inflammation and providing neuroprotection[@fischer2017]
Multiple Sclerosis: IL-15 contributes to autoimmune inflammation in CNS