Mechanisms of antigen-induced reversal of CNS inflammation in experimental demyelinating disease

被引：5

作者：

Li, Jian ^{[1
,2
]}

Lu, Lisen ^{[3
]}

Binder, Kyle ^{[1
,4
]}

Xiong, Jian ^{[2
]}

Ye, Lilin ^{[2
]}

Cheng, Yan H. ^{[1
,5
]}

Majri-Morrison, Sonia ^{[1
]}

Lu, Wei ^{[1
]}

Lee, Jae W. ^{[1
]}

Zhang, Zhihong ^{[1
,3
]}

Wu, Yu-zhang ^{[2
]}

Zheng, Lixin ^{[1
,5
]}

Lenardo, Michael J. ^{[1
,5
]}

机构：

[1] NIAID, Mol Dev Immune Syst Sect, Lab Immune Syst Biol, NIH, Bethesda, MD 20892 USA

[2] Third Mil Med Univ, Army Med Univ, Inst Immunol, Chongqing, Peoples R China

[3] Huazhong Univ Sci & Technol, Britton Chance Ctr Biomed Photon, MoE Key Lab Biomed Photon, Wuhan Natl Lab Optoelect, Wuhan 430074, Hubei, Peoples R China

[4] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD USA

[5] NIAID, NIAID Clin Genom Program, NIH, Bethesda, MD 20892 USA

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 09期

基金：

中国国家自然科学基金;

关键词：

EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; INDUCED CELL-DEATH; MULTIPLE-SCLEROSIS; MENINGEAL MACROPHAGES; NLRP3; INFLAMMASOME; GENE-THERAPY; T-CELLS; TOLERANCE;

D O I：

10.1126/sciadv.abo2810

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Autoimmune central nervous system (CNS) demyelinating diseases are a major public health burden and poorly controlled by current immunosuppressants. More precise immunotherapies with higher efficacy and fewer side effects are sought. We investigated the effectiveness and mechanism of an injectable myelin-based antigenic ed). We find that it suppresses mouse experimental autoimmune encephalomyelitis without major side effects. MMPt induces rapid apoptosis of the encephalitogenic T cells and suppresses inflammation in the affected CNS. Intravital microscopy shows that MMPt is taken up by perivascular F4/80+ cells but not conventional antigenpresenting dendritic cells, B cells, or microglia. MMPt-stimulated F4/80+ cells induce reactive T cell immobilization and apoptosis in situ, resulting in reduced infiltration of inflammatory cells and chemokine production. Our study reveals alternative mechanisms that explain how cognate antigen suppresses CNS inflammation and may be applicable for effectively and safely treating demyelinating diseases.

引用

页数：15