Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis.

Mucosal-associated invariant T (MAIT) cells express semi-invariant T cell receptors (TCR) for recognizing bacterial and yeast antigens derived from riboflavin metabolites presented on the non-polymorphic MHC class I-related protein 1 (MR1). Neuroinflammation in multiple sclerosis (MS) is likely initiated by autoreactive T cells and perpetuated by infiltration of additional immune cells, but the precise role of MAIT cells in MS pathogenesis remains unknown. Here, we use experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, and find an accumulation of MAIT cells in the inflamed central nervous system (CNS) enriched for MAIT17 (RORγt) and MAIT1/17 (T-betRORγt) subsets with inflammatory and protective features.

The NR4A2/VGF pathway fuels inflammation-induced neurodegeneration via promoting neuronal glycolysis.

A disturbed balance between excitation and inhibition (E/I balance) is increasingly recognized as a key driver of neurodegeneration in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. To understand how chronic hyperexcitability contributes to neuronal loss in MS, we transcriptionally profiled neurons from mice lacking inhibitory metabotropic glutamate signaling with shifted E/I balance and increased vulnerability to inflammation-induced neurodegeneration. This revealed a prominent induction of the nuclear receptor NR4A2 in neurons.

Sex- and species-specific contribution of CD99 to T cell costimulation during multiple sclerosis.

Background: Differences in immune responses between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests in more than twice as many women, making sex one of the most important risk factor. However, it is incompletely understood which genes contribute to sex differences in autoimmune incidence.

An automated and high-throughput-screening compatible pluripotent stem cell-based test platform for developmental and reproductive toxicity assessment of small molecule compounds.

The embryonic stem cell test (EST) represents the only validated and accepted in vitro system for the detection and classification of compounds according to their developmental and reproductive teratogenic potency. The widespread implementation of the EST, however, in particular for routine application in pharmaceutical development, has not been achieved so far. Several drawbacks still limit the high-throughput screening of potential drug candidates in this format: The long assay period, the use of non-homogeneous viability assays, the low throughput analysis of marker protein expression and the compatibility of the assay procedures to automation.