Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke.
Post-ischemic inflammation is an essential step in the progression of ischemic stroke. This review focuses on the function of infiltrating immune cells, macrophages, and T cells, in ischemic brain injury. The brain is a sterile organ; however, the activation of Toll-like receptor (TLR) 2 and TLR4 is pivotal in the beginning of post-ischemic inflammation. Some endogenous TLR ligands are released from injured brain cells, including high mobility group box 1 and peroxiredoxin family proteins, and activate the infiltrating macrophages and induce the expression of inflammatory cytokines. Following this step, T cells also infiltrate into the ischemic brain and mediate post-ischemic inflammation in the delayed phase. Various cytokines from helper T cells and γδT cells function as neurotoxic (IL-23/IL-17, IFN-γ) or neuroprotective (IL-10, IL-4) mediators. Novel neuroprotective strategies should therefore be developed through more detailed understanding of this process and the regulation of post-ischemic inflammation.
Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan.
Takashi
T
Shichita
Tetsuro
T
Ago
Masahiro
M
Kamouchi
Takanari
T
Kitazono
Akihiko
A
Yoshimura
Hiroaki
H
Ooboshi
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000209:etiology* / Q000628:therapy; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020521:Stroke / Q000150:complications / Q000276:immunology / Q000628:therapy; D051193:Toll-Like Receptors / Q000378:metabolism
D016207:Cytokines; D018696:Neuroprotective Agents; D051193:Toll-Like Receptors