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- Title
Brain Glycolipids Suppress T Helper Cells and Inhibit Autoimmune Demyelination.
- Authors
Mycko, Marcin P.; Sliwinska, Beata; Cichalewska, Maria; Cwiklinska, Hanna; Raine, Cedric S.; Selmaj, Krzysztof W.
- Abstract
TheCNSis considered animmuneprivileged site because its repertoire of highly immunogenic molecules remains unseen by theimmune system under normal conditions. However, the mechanism underlying the inhibition of immune reactions within the CNS environment is not known, particularly in regions containing myelin, which contains several potent proteins and lipids that are invariably recognized as foreign by immune system cells. Sulfatides constitute a major component of myelin glycolipids and are known to be capable of raising an immune response. In this study, the effect of sulfatides on mouse T cell function and differentiation was analyzed in vitro and in vivo. Wefound profound inhibition of sulfatide-dependent T cell proliferation which was particularly pronounced in naive T helper (Th) cells. The inhibitory effect of sulfatides on T cell function was CD1d-independent and was not related to apoptosis or necrosis but did involve the induction of anergy as confirmed by the upregulation of early growth response 2 transcription factor. A glycolipid 3-sulfate group was essential for the T cell suppression, and the T cell inhibition was galectin-4-dependent. Sulfatide stimulation in vitro led to prominent suppression of Th17 differentiation, and this was related to a decrease in susceptibility to disease in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis. Thus, we have defined a novel mechanism of negative regulation of T cell function by endogenous brain-derived glycolipids, a family of molecules traditionally deemphasized in favor of myelin proteins in studies of CNS autoimmunity.
- Subjects
T helper cells; ENCEPHALOMYELITIS; MYELIN proteins; SULFATIDES; DEMYELINATION; GLYCOLIPIDS; MULTIPLE sclerosis
- Publication
Journal of Neuroscience, 2014, Vol 34, Issue 25, p8646
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0885-14.2014