An atypical role for the myeloid receptor Mincle in central nervous system injury

Arumugam, T. V. et al. (2017) An atypical role for the myeloid receptor Mincle in central nervous system injury. Journal of Cerebral Blood Flow and Metabolism, 37(6), pp. 2098-2111. (doi: 10.1177/0271678X16661201) (PMID:27492949)

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Abstract

The C-type lectin Mincle is implicated in innate immune responses to sterile inflammation, but its contribution to associated pathologies is not well understood. Herein, we show that Mincle exacerbates neuronal loss following ischemic but not traumatic spinal cord injury. Loss of Mincle was beneficial in a model of transient middle cerebral artery occlusion but did not alter outcomes following heart or gut ischemia. High functional scores in Mincle KO animals using the focal cerebral ischemia model were accompanied by reduced lesion size, fewer infiltrating leukocytes and less neutrophilderived cytokine production than isogenic controls. Bone marrow chimera experiments revealed that the presence of Mincle in the central nervous system, rather than recruited immune cells, was the critical regulator of a poor outcome following transient middle cerebral artery occlusion. There was no evidence for a direct role for Mincle in microglia or neural activation, but expression in a subset of macrophages resident in the perivascular niche provided new clues on Mincle’s role in ischemic stroke.

Item Type:Articles
Additional Information:The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by Australian National Health & Medical Research Council (1057846, 1060538 and Fellowship to NAR), Spinal Cure Australia (Career Development Fellowship to MJR), the Australian Research Council, Singapore National Medical Research Council Collaborative Research Grant (NMRC-CBRG-0102/2016 to TA), the State Government of Victoria, the Australian Government and The University of Queensland.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macrae, Professor Mhairi and Dewar, Dr Deborah
Authors: Arumugam, T. V., Manzanero, S., Furtado, M., Biggins, P. J., Hsieh, Y.-H., Gelderblom, M., MacDonald, K. P., Salimova, E., Li, Y.-I., Korn, O., Dewar, D., Macrae, I. M., Ashman, R. B., Tang, S.-C., Rosenthal, N. A., Ruitenberg, M. J., Magnus, T., and Wells, C. A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Journal of Cerebral Blood Flow and Metabolism
Publisher:SAGE Publications
ISSN:0271-678X
ISSN (Online):1559-7016
Published Online:04 August 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Journal of Cerebral Blood Flow and Metabolism 37(6):2098-2111
Publisher Policy:Reproduced under a Creative Commons License

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