Interleukin 15 expression in the CNS: blockade of its activity prevents glial activation after an inflammatory injury.
Although reactive glia formation after neuronal degeneration or traumatic damage is one of the hallmarks of central nervous system (CNS) injury, we have little information on the signals that direct activation of resting glia. IL-15, a pro-inflammatory cytokine involved in regulating the response of T and B cells, may be also key for the regulation of early inflammatory events in the nervous system. IL-15 was expressed in the CNS, most abundantly in cerebellum and hippocampus, mainly in astrocytes and in some projection neurons. Using a rodent model of acute inflammatory injury [lipopolysaccharide (LPS) injection], we found enhanced expression of IL-15 in both reactive astroglia and microglia, soon after CNS injury. Blockade of IL-15 activity with an antibody to the cytokine, reversed activation of both glial types, suggesting that IL-15 has a major role in the generation of gliotic tissue and in the regulation of neuroimmune responses. Because IL-15 appears to modulate the inflammatory environment acutely generated after CNS injury, regulating IL-15 expression seems a clear antiinflammatory therapy to improve the outcome of neurodegenerative diseases and CNS trauma.
Gómez-Nicola
Diego
D
Functional and Systems Neurobiology Department, Cajal Institute, CSIC, Madrid, Spain.
Valle-Argos
Beatriz
B
Pita-Thomas
D Wolfgang
DW
Nieto-Sampedro
Manuel
M
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D004622:Embryo, Mammalian; D004660:Encephalitis / Q000139:chemically induced / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D014404:Tubulin / Q000378:metabolism
D000906:Antibodies; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D019409:Interleukin-15; D008070:Lipopolysaccharides; D014404:Tubulin; C462941:beta3 tubulin, mouse