Journal article
Axonally derived matrilin-2 induces proinflammatory responses that exacerbate autoimmune neuroinflammation
A Jonas, S Thiem, T Kuhlmann, R Wagener, A Aszodi, C Nowell, K Hagemeier, L Laverick, V Perreau, V Jokubaitis, B Emery, T Kilpatrick, H Butzkueven, M Gresle
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2014
DOI: 10.1172/JCI71385
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 neuronmacrophage cocultures revealed that exogenous MATN2 specifically signals through TLR4 and directly induces e..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
The authors would like to thank Elke Hoffmann and Claudia Kemming (Institute for Neuropathology, Muenster, Germany) for assisting with the human IHC processing. This work was supported by the National Multiple Sclerosis Society (US) (project grant RG3850A3/1 to H. Butzkueven and T. Kilpatrick); National Health and Medical Research Council Australia (project grant 509088 to H. Butzkueven and T. Kilpatrick, Career Development Award to H. Butzkueven, Centres of Research Excellence grant 1001216 providing fellowship support to M. Gresle); and a private donation form Kate and Gavin Rogers. R. Wagener was supported by the Deutsche Forschungsgemeinschaft grant WA 1338/2-6. B. Emery is supported by an National Health and Medical Research Council Australia career development fellowship. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.