Ischemic stroke is a common disease all over the world; however, the therapeutic strategy for ischemic stroke has been still limited. Here, we have identified the scavenger receptors, MSR1 and MARCO, as important receptors for the clearance of damage-associated molecular patterns (DAMPs) which trigger the sterile inflammation after ischemic stroke. Mafb, which is a pivotal transcription factor for macrophage differentiation, was also identified as an important transcription factor for the induction of MSR1-high pro-resolving macrophages in ischemic stroke. Thus, Mafb/MSR1 pathway promotes the resolution of cerebral post-ischemic inflammation. Finally, we demonstrated the novel pro-resolving effect of Am80, a retinoic acid receptor agonist, which enhanced Mafb/MSR1 pathway in macrophages infiltrated in ischemic brain. Our experimental results unvailed previously unknown mechanisms which prevented the excess inflammation and exacerbated pathologies after ischemic stroke.
Research Area “Elucidation and control of the mechanisms underlying chronic inflammation”
Research Theme “Investigation of immunoregulatory mechanisms in the chronic inflammation after cerebral injuries”
Shichita T, Ito M, Morita R, Komai K, Noguchi Y, Ooboshi H, Koshida R, Takahashi S, Kodama T and Yoshimura A. “MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1”, Nat Med, Published online April 10, 2017, doi: 10.1038/nm.4312.
Takashi Shichita, M.D., Ph.D.
Project Leader, Stroke Renaissance Project, Tokyo Metropolitan Institute of Medical Science
URL: http://www.igakuken.or.jp/project/detail/stroke-renaiss.html (Japanese)
Akihiko Yoshimura, Ph.D.
Professor, Department of Microbiology and Immunology, School of Medicine, Keio University
Life Innovation Group, Department of Innovation Research, JST: