期刊
JOURNAL OF AUTOIMMUNITY
卷 55, 期 -, 页码 51-62出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2014.05.007
关键词
Regulatory T cells; Immune tolerance; FoxP3; CD69
类别
资金
- Spanish Ministry of Economy and Competitiveness [SAF2011-27330, SAF2010-15106, SAF2011-25834]
- Comunidad de Madrid [INDISNET (S2010/BMD-2332)]
- RETICS Enfermedades Cardiovasculares from Instituto de Salud Carlos III [RD12/0042/0056]
- CNIC post-doctoral fellowship
- Spanish Ministry of Economy and Competitiveness
- Pro CNIC Foundation
- [ERC-2011-AdG294340-GENTRIS]
Although FoxP3(+) regulatory T cells are key players in the maintenance of immune tolerance and autoimmunity, the lack of specific markers constitute an obstacle to their use for immunotherapy protocols. In this study, we have investigated the role of the C-type lectin receptor CD69 in the suppressor function of Tregs and maintenance of immune tolerance towards harmless inhaled antigens. We identified a novel FoxP3(+)CD69(+) Treg subset capable to maintain immune tolerance and protect to developing inflammation. Although CD69(+) and CD69(-)FoxP3(+) Tregs exist in homeostasis, only CD69-expressing Tregs express high levels of CTLA-4, ICOS, CD38 and GITR suppression-associated markers, secrete high amounts of TGFO and have potent suppressor activity. This activity is regulated by STAT5 and ERK signaling pathways and is impaired by antibody-mediated down-regulation of CD69 expression. Moreover, immunotherapy with FoxP3(+)CD69(+) Tregs restores the homeostasis in Cd69(-/-) mice, that fail to induce tolerance, and is also highly proficient in the prevention of inflammation. The identification of the FoxP3(+)CD69(+) Treg subset paves the way toward the development of new therapeutic strategies to control immune homeostasis and autoimmunity. (C) 2014 Elsevier Ltd. All rights reserved.
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