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Workshop 6: Microglial Activators and Inactivators. Mechanisms of induction and repression of CD40 in microglia/macrophages
Author(s) -
Benveniste E.,
Nguyen V. T.,
Wesemann D.,
O'Keefe G. M.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00061.x
Subject(s) - microglia , cd40 , neuroinflammation , antigen presentation , biology , immune system , neuroscience , microbiology and biotechnology , immunology , inflammation , macrophage , t cell , cytotoxic t cell , biochemistry , in vitro
Microglia and macrophages are important antigen‐presenting cells (APCs) in the central nervous system (CNS). By virtue of their ability to express class II MHC antigens and costimulatory molecules such as CD40 and B7, microglia/macrophages promote Th1 cell activation and subsequent immune/inflammatory responses within the CNS. We have previously demonstrated that IFN‐γ is the most potent inducer of CD40 expression on microglia. Our more recent studies have focused on the molecular basis of IFN‐γ induced CD40 expression, and mechanisms by which this gene can be inhibited. The suppressive effects of IL‐4 on CD40 expression will be discussed, as will the involvement of SH2 containing proteins called SOCS (for Suppressors Of Cytokine Signalling). Expression of CD40 by activated microglia/macrophages may contribute to the complex neuroimmunologic cascades that result in inflammation, demyelination and neuronal dysfunction. As such, understanding the mechanisms of inhibition of this molecule will be beneficial in diseases such as multiple sclerosis, HIV‐1 associated dementia and Alzheimer's disease.