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Induction of IL‐33 expression and activity in central nervous system glia
Author(s) -
Hudson Chad A.,
Christophi George P.,
Gruber Ross C.,
Wilmore Joel R.,
Lawrence David A.,
Massa Paul T.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1207830
Subject(s) - biology , astrocyte , innate immune system , immune system , neuroglia , encephalomyelitis , central nervous system , microbiology and biotechnology , cytokine , microglia , immunology , neuroinflammation , mast cell , inflammation , neuroscience
IL‐33 is a novel member of the IL‐1 cytokine family and a potent inducer of type 2 immunity, as mast cells and Th2 CD4+ T cells respond to IL‐33 with the induction of type 2 cytokines such as IL‐13. IL‐33 mRNA levels are extremely high in the CNS, and CNS glia possess both subunits of the IL‐33R, yet whether IL‐33 is produced by and affects CNS glia has not been studied. Here, we demonstrate that pathogen‐associated molecular patterns (PAMPs) significantly increase IL‐33 mRNA and protein expression in CNS glia. Interestingly, IL‐33 was localized to the nucleus of astrocytes. Further, CNS glial and astrocyte‐enriched cultures treated with a PAMP followed by an ATP pulse had significantly higher levels of supernatant IL‐1β and IL‐33 than cultures receiving any single treatment (PAMP or ATP). Supernatants from PAMP + ATP‐treated glia induced the secretion of IL‐6, IL‐13, and MCP‐1 from the MC/9 mast cell line in a manner similar to exogenous recombinant IL‐33. Further, IL‐33 levels and activity were increased in the brains of mice infected with the neurotropic virus Theiler's murine encephalomyelitis virus. IL‐33 also had direct effects on CNS glia, as IL‐33 induced various innate immune effectors in CNS glia, and this induction was greatly amplified by IL‐33‐stimulated mast cells. In conclusion, these results implicate IL‐33‐producing astrocytes as a potentially critical regulator of innate immune responses in the CNS.