A pain-mediated neural signal induces relapse in murine autoimmune encephalomyelitis, a multiple sclerosis model

被引：43

作者：

Arima, Yasunobu ^{[1
,2
]}

Kamimura, Daisuke ^{[1
,2
]}

Atsumi, Toru ^{[1
,2
]}

Harada, Masaya ^{[1
,2
]}

Kawamoto, Tadafumi ^{[3
]}

Nishikawa, Naoki ^{[1
,2
,4
]}

Stofkova, Andrea ^{[1
,2
]}

Ohki, Takuto ^{[1
,2
]}

Higuchi, Kotaro ^{[1
,2
]}

Morimoto, Yuji ^{[4
]}

Wieghofer, Peter ^{[5
]}

Okada, Yuka ^{[6
]}

Mori, Yuki ^{[7
]}

Sakoda, Saburo ^{[8
]}

Saika, Shizuya ^{[6
]}

Yoshioka, Yoshichika ^{[7
]}

Komuro, Issei ^{[9
]}

Yamashita, Toshihide ^{[10
]}

Hirano, Toshio ^{[11
]}

Prinz, Marco ^{[12
]}

Murakami, Masaaki ^{[1
,2
]}

机构：

[1] Hokkaido Univ, Grad Sch Med, Inst Med Genet, Div Mol Neuroimmunol, Sapporo, Hokkaido, Japan

[2] Osaka Univ, Grad Sch Med, WPI Immunol Frontier Res Ctr, Lab Dev Immunol,Grad Sch Frontier Biosci, Osaka, Japan

[3] Tsurumi Univ, Dept Dent, Yokohama, Kanagawa, Japan

[4] Hokkaido Univ, Grad Sch Med, Dept Anesthesiol & Crit Care Med, Sapporo, Hokkaido, Japan

[5] Univ Freiburg, Fac Biol, Inst Neuropathol, Hugstetter Str 55, D-79106 Freiburg, Germany

[6] Wakayama Med Univ, Dept Ophthalmol, Wakayama, Japan

[7] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Biofunct Imaging, Osaka, Japan

[8] Natl Hosp Org Toneyama Hosp, Dept Neurol, Osaka, Japan

[9] Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Tokyo, Japan

[10] Osaka Univ, Grad Sch Frontier Biosci, Grad Sch Med, Lab Mol Neurosci, Osaka, Japan

[11] Osaka Univ, Osaka, Japan

[12] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, Hugstetter Str 55, D-79106 Freiburg, Germany

来源：

ELIFE | 2015年 / 4卷

基金：

日本学术振兴会;

关键词：

CD8(+) T-CELLS; INFLAMMATION AMPLIFIER; POSITIVE-FEEDBACK; IL-6; AMPLIFIER; IMMUNE CELLS; PREVALENCE; ACTIVATION; MECHANISMS; INTERLEUKIN-6; DEPRESSION;

D O I：

10.7554/eLife.08733

中图分类号：

Q [生物科学];

学科分类号：

090105 [作物生产系统与生态工程];

摘要：

Although pain is a common symptom of various diseases and disorders, its contribution to disease pathogenesis is not well understood. Here we show using murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), that pain induces EAE relapse. Mechanistic analysis showed that pain induction activates a sensory-sympathetic signal followed by a chemokine-mediated accumulation of MHC class II+CD11b+ cells that showed antigen-presentation activity at specific ventral vessels in the fifth lumbar cord of EAE-recovered mice. Following this accumulation, various immune cells including pathogenic CD4+ T cells recruited in the spinal cord in a manner dependent on a local chemokine inducer in endothelial cells, resulting in EAE relapse. Our results demonstrate that a pain-mediated neural signal can be transformed into an inflammation reaction at specific vessels to induce disease relapse, thus making this signal a potential therapeutic target. DOI: 10.7554/eLife.08733.001

引用

页数：23

共 54 条

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Regional Neural Activation Defines a Gateway for Autoreactive T Cells to Cross the Blood-Brain Barrier [J].