Wnt/beta-Catenin Signaling Induces Integrin alpha 4 beta 1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F17%3A00100351" target="_blank" >RIV/00216224:14740/17:00100351 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.jimmunol.org/content/199/9/3031" target="_blank" >http://www.jimmunol.org/content/199/9/3031</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4049/jimmunol.1700247" target="_blank" >10.4049/jimmunol.1700247</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Wnt/beta-Catenin Signaling Induces Integrin alpha 4 beta 1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice

Popis výsledku v původním jazyce

The mechanisms leading to autoimmune and inflammatory diseases in the CNS have not been elucidated. The environmental triggers of the aberrant presence of CD4(+) T cells in the CNS are not known. In this article, we report that abnormal beta-catenin expression in T cells drives a fatal neuroinflammatory disease in mice that is characterized by CNS infiltration of T cells, glial activation, and progressive loss of motor function. We show that enhanced beta-catenin expression in T cells leads to aberrant and Th1-biased T cell activation, enhanced expression of integrin alpha 4 beta 1, and infiltration of activated T cells into the spinal cord, without affecting regulatory T cell function. Importantly, expression of beta-catenin in mature naive T cells was sufficient to drive integrin alpha 4 beta 1 expression and CNS migration, whereas pharmacologic inhibition of integrin alpha 4 beta 1 reduced the abnormal T cell presence in the CNS of beta-catenin-expressing mice. Together, these results implicate deregulation of the Wnt/beta-catenin pathway in CNS inflammation and suggest novel therapeutic strategies for neuroinflammatory disorders.

Název v anglickém jazyce

Wnt/beta-Catenin Signaling Induces Integrin alpha 4 beta 1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice

Popis výsledku anglicky

The mechanisms leading to autoimmune and inflammatory diseases in the CNS have not been elucidated. The environmental triggers of the aberrant presence of CD4(+) T cells in the CNS are not known. In this article, we report that abnormal beta-catenin expression in T cells drives a fatal neuroinflammatory disease in mice that is characterized by CNS infiltration of T cells, glial activation, and progressive loss of motor function. We show that enhanced beta-catenin expression in T cells leads to aberrant and Th1-biased T cell activation, enhanced expression of integrin alpha 4 beta 1, and infiltration of activated T cells into the spinal cord, without affecting regulatory T cell function. Importantly, expression of beta-catenin in mature naive T cells was sufficient to drive integrin alpha 4 beta 1 expression and CNS migration, whereas pharmacologic inhibition of integrin alpha 4 beta 1 reduced the abnormal T cell presence in the CNS of beta-catenin-expressing mice. Together, these results implicate deregulation of the Wnt/beta-catenin pathway in CNS inflammation and suggest novel therapeutic strategies for neuroinflammatory disorders.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of immunology

ISSN

0022-1767

e-ISSN

—

Svazek periodika

199

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

3031-3041

Kód UT WoS článku

000413466400005

EID výsledku v databázi Scopus

2-s2.0-85032033490