Axonally derived matrilin-2 induces proinflammatory responses that exacerbate autoimmune neuroinflammation.

ABSTRACT: In patients with multiple sclerosis (MS) and mice with experimental autoimmune encephalomyelitis (EAE), inflammatory axonal injury is a major determinant of disability; however, the drivers of this injury are incompletely understood. Here, we used the EAE model and determined that the extracellular matrix protein matrilin-2 (MATN2) is an endogenous neuronal molecule that is regulated in association with inflammatory axonal injury. Compared with WT mice, mice harboring a deletion of Matn2 exhibited reduced disease severity and axon damage following induction of EAE. Evaluation of neuron-macrophage cocultures revealed that exogenous MATN2 specifically signals through TLR4 and directly induces expression of proinflammatory genes in macrophages, promoting axonal damage. Moreover, the MATN2-ind

SUBMITTER: Jonas A 

PROVIDER: S-EPMC4347228 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature