Regulation of Inflammation after Stroke by Macrophages and Regulatory T Cells


Identification: Yoshimura, Akihiko


Description

Regulation of Inflammation after Stroke by Macrophages and Regulatory T Cells
 
Akihiko Yoshimura1, Minako Ito 1, Takashi Shichita2
1Department of Microbiology and Immunology, Keio University School of Medicine,
2Stroke Renaissance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
 
Sroke or brain ischemia is one of the major causes of death and disability worldwide. Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. In a mouse stroke model, we have reported that IL-1β, IL-23 and IL-17 play essential roles in infarct volume growth within 1-4 days after brain ischemia stroke model. Extracellular DAMPs (damage-associated molecular patterns) including Prxs released from dead cells activate infiltrated macrophages on day 1 through a Toll-like receptor 2 (TLR2) and TLR4 -dependent mechanism, then stimulate IL-1β and IL-23 production. Then these inflammatory cytokines induce IL-17 from γδT cells and exacerbate ischemic brain damage on day 3-4. After day 3, DAMPs are cleared by macrophages through type A scavenger receptors, which is an important process for the resolution of brain inflammation. Macrophages expressing high levels of scavenger receptors are also involved in neural repair by producing IGF-1. After day 7, inflammation looks over and the involvement of immune cells during chronic phage (after day 14) of stroke has not been investigated. However, two weeks after a stroke, a massive accumulation of Tregs occurs in the brain. Gene expression analysis revealed that brain Tregs related to Tregs in other tissues such as adipose tissue and muscle, however, brain Tregs are apparently different from them and express several unique genes related to the nerve system. Brain Tregs regulate astrocyte activation and reduce neural damages. Our findings suggest that M2 type macrophages and Tregs, and their products may provide new therapeutic opportunities for neuronal protection against stroke.
 
References
Shichita T, et al. Nature Med. 2017 Jun;23(6):723-732. doi: 10.1038/nm.4312
Ito M, et al.Nat Commun. 2015 Jun 10;6:7360. doi: 10.1038/ncomms8360.
Shichita T, et al. Nature Med. 2012 Jun;18(6):911-7. doi: 10.1038/nm.2749.
Shichita T, et al.  Nature Med. 2009 Aug;15(8):946-50. doi: 10.1038/nm.1999.
 

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