Document Detail


Foxp3+-inducible regulatory T cells suppress endothelial activation and leukocyte recruitment.
MedLine Citation:
PMID:  21873519     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ability of regulatory T cells (Treg) to traffic to sites of inflammation supports their role in controlling immune responses. This feature supports the idea that adoptive transfer of in vitro expanded human Treg could be used for treatment of immune/inflammatory diseases. However, the migratory behavior of Treg, as well as their direct influence at the site of inflammation, remains poorly understood. To explore the possibility that Treg may have direct anti-inflammatory influences on tissues, independent of their well-established suppressive effects on lymphocytes, we studied the adhesive interactions between mouse Treg and endothelial cells, as well as their influence on endothelial function during acute inflammation. We show that Foxp3(+) adaptive/inducible Treg (iTreg), but not naturally occurring Treg, efficiently interact with endothelial selectins and transmigrate through endothelial monolayers in vitro. In response to activation by endothelial Ag presentation or immobilized anti-CD3ε, Foxp3(+) iTreg suppressed TNF-α- and IL-1β-mediated endothelial selectin expression and adhesiveness to effector T cells. This suppression was contact independent, rapid acting, and mediated by TGF-β-induced activin receptor-like kinase 5 signaling in endothelial cells. In addition, Foxp3(+) iTreg adhered to inflamed endothelium in vivo, and their secretion products blocked acute inflammation in a model of peritonitis. These data support the concept that Foxp3(+) iTreg help to regulate inflammation independently of their influence on effector T cells by direct suppression of endothelial activation and leukocyte recruitment.
Authors:
Elena Maganto-García; De-Xiu Bu; Margarite L Tarrio; Pilar Alcaide; Gail Newton; Gabriel K Griffin; Kevin J Croce; Francis W Luscinskas; Andrew H Lichtman; Nir Grabie
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-26
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  187     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-21     Completed Date:  2011-11-22     Revised Date:  2013-02-08    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3521-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Adhesion / immunology
Cell Separation
Chemotaxis, Leukocyte / immunology*
Endothelium, Vascular / immunology*,  metabolism
Flow Cytometry
Forkhead Transcription Factors / immunology,  metabolism
Gene Knock-In Techniques
Inflammation / immunology*
Mice
Mice, Inbred C57BL
Signal Transduction / immunology*
T-Lymphocytes, Regulatory / immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
1K08HL086672/HL/NHLBI NIH HHS; HL087282/HL/NHLBI NIH HHS; K08 HL086672/HL/NHLBI NIH HHS; K08 HL086672-02/HL/NHLBI NIH HHS; K08 HL086672-03/HL/NHLBI NIH HHS; K08 HL086672-04/HL/NHLBI NIH HHS; K08 HL086672-05/HL/NHLBI NIH HHS; K99RO HL094706/HL/NHLBI NIH HHS; P01 HL036028-25/HL/NHLBI NIH HHS; P01 HL036028-26/HL/NHLBI NIH HHS; P01 HL036028-27/HL/NHLBI NIH HHS; P0HL36028/HL/NHLBI NIH HHS; R00 HL094706/HL/NHLBI NIH HHS; R01 HL087282-01/HL/NHLBI NIH HHS; R01 HL087282-02/HL/NHLBI NIH HHS; R01 HL087282-03/HL/NHLBI NIH HHS; R01 HL087282-04/HL/NHLBI NIH HHS; R01 HL087282-05/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse
Comments/Corrections

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