Downregulation of transforming growth factor-beta2 facilitates inflammation in the central nervous system by reciprocal astrocyte/microglia interactions.

Authors: Siglienti, I  Chan, A  Kleinschnitz, C  Jander, S  Toyka, KV  Gold, R  Stoll, G 
Citation: Siglienti I, etal., J Neuropathol Exp Neurol. 2007 Jan;66(1):47-56.
Pubmed: (View Article at PubMed) PMID:17204936
DOI: Full-text: DOI:10.1097/nen.0b013e31802d47b4

The central nervous system is an immune privileged organ in which inflammatory reactions are normally downregulated by mechanisms that are not completely understood. Transforming growth factor (TGF)-beta2 is constitutively expressed in the adult central nervous system and little is known about its regulation and modulatory role during neuroinflammation. In this study, we show that TGFbeta2 mRNA and protein are downregulated in the acute phase of chronic relapsing experimental autoimmune encephalomyelitis, whereas the homologous cytokine TGFbeta1 is upregulated. To further characterize regulatory mechanisms, we resorted to an in vitro glial cell culture system. The proinflammatory cytokines IFNgamma and TNFalpha suppressed TGFbeta2 secretion by astrocytes, the major intracerebral producers of TGFbeta2. On the cellular level, activated microglia inhibited TGFbeta2 secretion but induced TGFbeta1 through soluble factors. On the other hand, TGFbeta2 influenced antigen-presenting cell functions of microglia by downregulating major histocompatibility complex class II expression and costimulatory/adhesion molecules, and thereby inhibited myelin basic protein-specific T cell proliferation. These data suggest that TGFbeta2 plays a central role in maintenance of the immune privilege of the central nervous system. Downregulation of astrocytic TGFbeta2 by T cell- and microglia-secreted cytokines appears to be a critical step in providing the grounds for acute and chronic neuroinflammation.


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CRRD ID: 2302088
Created: 2008-11-18
Species: All species
Last Modified: 2008-11-18
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.