Mouse brain microglia express interleukin-15 and its multimeric receptor complex functionally coupled to Janus kinase activity.
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.
Hanisch
U K
UK
Max Delbrück Center for Molecular Medicine, Cellular Neurosciences, Robert-Rössle-Strasse 10, 13122 Berlin-Buch, Germany. uh@nero.glia.mdc-berlin.de
Lyons
S A
SA
Prinz
M
M
Nolte
C
C
Weber
J R
JR
Kettenmann
H
H
Kirchhoff
F
F
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D053613:Janus Kinase 1; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D009569:Nitric Oxide; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; C507906:Jak1 protein, rat; D053613:Janus Kinase 1; D002118:Calcium