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NLRX1 inhibits the early stages of CNS inflammation and prevents the onset of spontaneous autoimmunity.

PLoS biology (2019-09-17)
Marjan Gharagozloo, Shaimaa Mahmoud, Camille Simard, Kenzo Yamamoto, Diwakar Bobbala, Subburaj Ilangumaran, Matthew D Smith, Albert Lamontagne, Samir Jarjoura, Jean-Bernard Denault, Véronique Blais, Louis Gendron, Carles Vilariño-Güell, A Dessa Sadovnick, Jenny P Ting, Peter A Calabresi, Abdelaziz Amrani, Denis Gris
RÉSUMÉ

Nucleotide-binding, leucine-rich repeat containing X1 (NLRX1) is a mitochondria-located innate immune sensor that inhibits major pro-inflammatory pathways such as type I interferon and nuclear factor-κB signaling. We generated a novel, spontaneous, and rapidly progressing mouse model of multiple sclerosis (MS) by crossing myelin-specific T-cell receptor (TCR) transgenic mice with Nlrx1-/- mice. About half of the resulting progeny developed spontaneous experimental autoimmune encephalomyelitis (spEAE), which was associated with severe demyelination and inflammation in the central nervous system (CNS). Using lymphocyte-deficient mice and a series of adoptive transfer experiments, we demonstrate that genetic susceptibility to EAE lies within the innate immune compartment. We show that NLRX1 inhibits the subclinical stages of microglial activation and prevents the generation of neurotoxic astrocytes that induce neuronal and oligodendrocyte death in vitro. Moreover, we discovered several mutations within NLRX1 that run in MS-affected families. In summary, our findings highlight the importance of NLRX1 in controlling the early stages of CNS inflammation and preventing the onset of spontaneous autoimmunity.

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Albumine de sérum bovin, fatty acid free, low endotoxin, lyophilized powder, BioReagent, suitable for cell culture, ≥96% (agarose gel electrophoresis)