Document Type

Article

Publication Date

Spring 4-17-2012

Abstract

Multiple sclerosis (MS) is a demyelinating autoimmune disease mediated by infiltration of T cells into the central nervous system after compromise of the blood-brain barrier. We have previously shown that administration of tuftsin, a macrophage/microglial activator, dramatically improves the clinical course of experimental autoimmune encephalomyelitis (EAE), a well-established animal model for MS. Tuftsin administration correlates with upregulation of the immunosuppressive Helper-2 Tcell (Th2) cytokine transcription factor GATA-3. We now show that tuftsin-mediated microglial activation results in shifting microglia to an anti-inflammatory phenotype. Moreover, the T cell phenotype is shifted towards immunoprotection after exposure to tuftsin-treated activated microglia; specifically, downregulation of pro-inflammatory Th1 responses is triggered in conjunction with upregulation of Th2-specific responses and expansion of immunosuppressive regulatory T cells (Tregs). Finally, tuftsin-shifted T cells, delivered into animals via adoptive transfer, reverse the pathology observed in mice with established EAE. Taken together, our findings demonstrate that tuftsin decreases the proinflammatory environment of EAE and may represent a therapeutic opportunity for treatment of MS.

Comments

Published in PLoS ONE 7(4): e34933. http://dx.doi.org/10.1371/journal.pone.0034933 Shared via Creative Commons CC BY 2.0.

Funding: This work was supported by National Institutes of Health (NIH) R01NS42168, National Multiple Sclerosis Society (NMSS) CA1044A1 and National Science Foundation (NSF) 3MT IGERT. The mass spectrometer used in this study was funded by the shared instrument grant (NIH/NCRR 1 S10 RR023680-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.