Mouse brain microglia express interleukin-15 and its multimeric receptor complex functionally coupled to Janus kinase...

Area of Science:

• Neuroimmunology
• Cellular and Molecular Neuroscience

Background:

• Interleukin-2 (IL-2) has suggested neuroregulatory roles, but its CNS expression is limited.
• IL-2 and Interleukin-15 (IL-15) share receptor subunits (IL-2Rbeta and IL-2Rgamma) for signaling in immune cells.

Purpose of the Study:

• To investigate the presence and function of IL-15 and its receptor system in the central nervous system (CNS).
• To determine if microglia, the resident immune cells of the brain, express IL-15 and its associated receptors.

Main Methods:

• RNA and protein detection methods were used to identify IL-15 and its receptor components in the mouse brain.
• Single-cell analysis was performed to localize expression within microglia.
• Functional assays assessed IL-15's effects on microglial nitric oxide production and cell growth.

Main Results:

• Constitutive expression of IL-15, IL-15Ralpha, IL-2Rbeta, and IL-2Rgamma was detected in developing and adult mouse brains.
• IL-15 and its receptor components were found to be expressed by microglia.
• IL-15 signaling in microglia involves Janus kinase 1 (JAK1) activity.
• Low doses of IL-15 modulated microglial nitric oxide production and supported cell growth, indicating autocrine functions.

Conclusions:

• IL-15 is constitutively expressed in the brain and produced by microglia.
• Microglial IL-15 may play a significant role in CNS functions, potentially mediating roles previously attributed to IL-2.