RT Journal Article
SR Electronic
T1 An atypical role for the myeloid receptor Mincle in CNS injury
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 044602
DO 10.1101/044602
A1 Thiruma V. Arumugam
A1 Silvia Manzanero
A1 Milena Furtado
A1 Patrick J. Biggins
A1 Yu-Hsuan Hsieh
A1 Mathias Gelderblom
A1 Kelli PA MacDonald
A1 Ekaterina Salimova
A1 Yu-I Li
A1 Othmar Korn
A1 Deborah Dewar
A1 I Mhairi Macrae
A1 Robert B. Ashman
A1 Sung-Chun Tang
A1 Nadia A. Rosenthal
A1 Marc J. Ruitenberg
A1 Tim Magnus
A1 Christine A. Wells
YR 2016
UL http://biorxiv.org/content/early/2016/03/19/044602.abstract
AB Mincle is a C-type lectin known to play a role in innate immune responses to sterile inflammation, but its contribution to pathologies following an ischemic or traumatic injury is not well understood. In the current study we demonstrate a key role for Mincle in ischemic (i.e. transient middle cerebral artery occlusion) but not traumatic central nervous system injury; absence of Mincle also did not significantly alter the extent of tissue damage or functional outcome in peripheral models of ischemic tissue injury. In the stroke model mice lacking Mincle displayed significantly improved functional outcome from focal cerebral ischemia. The functional improvements in Mincle KO animals were accompanied by reduced infiltration of neutrophils and lower levels of proinflammatory cytokines in recruited peripheral blood cells. Bone marrow chimera experiments revealed that presence of Mincle in the central nervous system, but not peripheral immune cells, was the critical regulator of a poor outcome following transient focal cerebral ischemia, however we exclude a direct role for Mincle in microglia or neural activation. We demonstrate that Mincle lacks widespread expression in the brain, but is specifically associated with macrophages resident in the perivascular niche. These findings implicate Mincle in the initiation, extent and severity of local responses to ischemic injury in the brain, but not peripheral tissues. Mincle signalling therefore offers a novel therapeutic target in the quest to limit damage after stroke.Sources of support: Australian National Health & Medical Research Council [1057846, 1060538 and Fellowship to NAR], SpinalCure Australia (Career Development Fellowship to MJR), the Australian Research Council, the State Government of Victoria, the Australian Government and The University of Queensland.