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Mouse brain microglia express interleukin-15 and its multimeric receptor complex functionally coupled to Janus kinase
U K Hanisch1, S A Lyons, M Prinz
1Max Delbrück Center for Molecular Medicine, Cellular Neurosciences, Robert-Rössle-Strasse 10, 13122 Berlin-Buch, Germany. uh@nero.glia.mdc-berlin.de
Abstract:
The cytokine, interleukin (IL)-15, and the T cell growth factor, IL-2, exhibit a similar spectrum of immune effects and share the IL-2 receptor (IL-2R) subunits IL-2Rbeta and IL-2Rgamma for signaling in hematopoietic cells. Numerous neuroregulatory activities of IL-2 have been suggested, but its expression in the normal central nervous system (CNS) is apparently very low and regionally restricted. We show by RNA and protein detection that IL-15, its specific receptor molecule, IL-15Ralpha, and the signal-transducing receptor subunits, IL-2Rbeta and IL-2Rgamma, are constitutively present in various regions of the developing and adult mouse brain. We further demonstrate, also at the single-cell level, that IL-15 and the components for IL-15Ralpha/IL-2Rbetagamma receptors are expressed by microglia. Tyrosine phosphorylation data are presented showing that IL-15 signaling in microglia involves Janus kinase 1 activity. At doses of 0.1-10 ng/ml, IL-15 affected functional properties of these cells, such as the production of nitric oxide, and supported their growth in culture, suggestive of a role as an autocrine growth factor. Microglial IL-15 could thus play a pivotal role in the CNS and may participate in certain CNS and neuroendocrine functions previously ascribed to IL-2.
Insights
Interleukin-15 (IL-15) and its receptor components are present in the mouse brain, specifically in microglia. IL-15 influences microglial function, suggesting a novel role in central nervous system (CNS) regulation.
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.