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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2806-2814.
Prepublished online as a Blood First Edition Paper on December 19, 2006; DOI 10.1182/blood-2006-06-030213.


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Submitted June 22, 2006
Accepted November 22, 2006

Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activation

Stephanie Coupel, Anne Moreau, Mohamed Hamidou, Vaclav Horejsi, Jean-Paul Soulillou, and Beatrice Charreau*

Institut National de la Sante Et de la Recherche Medicale, Unit 643, Institut de Transplantation et de Recherche en Transplantation, Nantes, France
CHU Hotel-Dieu, Service d'Anatomo-Pathologie, Nantes, France
CHU Hotel-Dieu, Service de medecine interne, Nantes, France
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Praha, Czech Republic

* Corresponding author; email: beatrice.charreau{at}univ-nantes.fr.

HLA-E belongs, with HLA-G and HLA-F, to the nonclassic MHC class I (Ib) molecules, broadly defined by a limited polymorphism and a restricted pattern of cellular expression. In contrast to HLA-G, the expression and function of HLA-E and HLA-F in physiological and pathologic processes remain poorly established. In the present study, we show that HLA-E protein expression, in normal human nonlymphoid organs is mainly restricted to endothelial cells (ECs). HLA-E is also basally expressed by B and T lymphocytes, NK cells and by macrophages. We demonstrate that TNF{alpha}, IL-1{beta} and IFN{gamma} up-regulate the cell surface expression of HLA-E on ECs in vitro and induce the release of soluble HLA-E (sHLA-E). HLA-E up-regulation protects IFN{gamma}-activated ECs from NK-mediated cell lysis while sHLA-E protects bystander cells. Finally, sHLA-E is not detected in normal sera and increased serum levels correlate with disease activity in patients with anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. Thus, HLA-E expression and release of sHLA-E are features of EC activation and emphasize immunoregulatory functions of the endothelium. The present identification of soluble HLA-E molecules may have important implications in understanding the pathogenesis of immune-mediated vascular diseases and for the diagnosis and monitoring of patients.


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