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

被引：245

作者：

Arima, Yasunobu ^{[1
,2
]}

Harada, Masaya ^{[1
,2
]}

Kamimura, Daisuke ^{[1
,2
]}

Park, Jin-Haeng ^{[1
,2
]}

Kawano, Fuminori ^{[3
]}

Yull, Fiona E. ^{[4
]}

Kawamoto, Tadafumi ^{[6
]}

Iwakura, Yoichiro ^{[7
]}

Betz, Ulrich A. K. ^{[8
]}

Marquez, Gabriel ^{[9
]}

Blackwell, Timothy S. ^{[4
,5
]}

Ohira, Yoshinobu ^{[3
]}

Hirano, Toshio ^{[1
,2
,10
]}

Murakami, Masaaki ^{[1
,2
]}

机构：

[1] Osaka Univ, Lab Dev Immunol, JST CREST, Grad Sch Frontier Biosci,Grad Sch Med, Suita, Osaka 5650871, Japan

[2] Osaka Univ, WPI Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Dept Hlth & Sports Sci, Grad Sch Med, Osaka 5600043, Japan

[4] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA

[5] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA

[6] Tsurumi Univ, Dept Dent Med, Radioisotope Res Inst, Yokohama, Kanagawa 2308501, Japan

[7] Univ Tokyo, Ctr Expt Med & Syst Biol, Inst Med Sci, Tokyo 1088639, Japan

[8] Portfolio Dev Merck Serono, Merck KGaA, D-64293 Darmstadt, Germany

[9] Natl Ctr Biotechnol CNB CSIC, Madrid 28049, Spain

[10] RIKEN Res Ctr Allergy & Immunol, Lab Cytokine Signaling, Yokohama, Kanagawa 2300045, Japan

来源：

CELL | 2012年 / 148卷 / 03期

关键词：

EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; AUTOIMMUNE ENCEPHALOMYELITIS; ADOPTIVE TRANSFER; SPLEEN-CELLS; IN-VITRO; IMMUNE; PROLIFERATION; INTERLEUKIN-6; SYSTEM; MICE;

D O I：

10.1016/j.cell.2012.01.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Although it is believed that neural activation can affect immune responses, very little is known about the neuroimmune interactions involved, especially the regulators of immune traffic across the blood-brain barrier which occurs in neuroimmune diseases such as multiple sclerosis (MS). Using a mouse model of MS, experimental autoimmune encephalomyelitis, we show that autoreactive T cells access the central nervous system via the fifth lumbar spinal cord. This location is defined by IL-6 amplifier-dependent upregulation of the chemokine CCL20 in associated dorsal blood vessels, which in turn depends on gravity-induced activation of sensory neurons by the soleus muscle in the leg. Impairing soleus muscle contraction by tail suspension is sufficient to reduce localized chemokine expression and block entry of pathogenic T cells at the fifth lumbar cord, suggesting that regional neuroimmune interactions may offer therapeutic targets for a variety of neurological diseases.

引用

页码：447 / 457

页数：11

共 40 条

[1] Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects [J].