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Hum. Reprod. Advance Access originally published online on October 18, 2007
Human Reproduction 2008 23(1):144-152; doi:10.1093/humrep/dem326
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Human decidual stromal cells express HLA-G Effects of cytokines and decidualization

Osmany Blanco1, Irene Tirado1, Raquel Muñoz-Fernández1, Ana Clara Abadía-Molina1, Jose Marcos García-Pacheco2, Jose Peña3 and Enrique G. Olivares1,4,5

1 Departamento de Bioquímica, Biología Molecular 3 e Inmunología, Facultad de Medicina, Unidad de Inmunología, Instituto de Biopatología y Medicina Regenerativa, Universidad de Granada, 18012- Granada, Spain 2 Servicio de Inmunología, Hospital Virgen de la Arreixaca, Murcia, Spain 3 Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Spain 4 Servicio de Análisis Clínicos, Hospital Universitario ‘San Cecilio’, Servicio Andaluz de Salud, Granada, Spain

5 Correspondence address. Tel: +34-958-243107; Fax: +34-958-249015; E-mail: engarcia{at}ugr.es

BACKGROUND: Decidual stromal cells (DSC) are the main cellular component of the decidua, the maternal tissue in close contact with fetal trophoblast. Although of mesenchymal origin, DSC exert numerous immune functions that seem to be relevant for the immunological relationship between the mother and fetus. HLA-G, an antigen preferentially expressed by trophoblast, appears to participate in the immune tolerance by the mother of the semiallogeneic fetus.

METHODS AND RESULTS: We show by flow cytometry, fluorescence microscopy, western blotting and RT–PCR that DSC isolated and maintained in culture express HLA-G weakly but consistently. We also detected this antigen by flow cytometry in fresh DSC. Interleukin (IL)-10, a cytokine associated with normal pregnancy, increased the expression of HLA-G by DSC (P < 0.00001), whereas IL-2, a cytokine involved in spontaneous abortion, showed no effect. Decidualization by progesterone and cAMP also up-regulated the expression of HLA-G by DSC (P < 0.001). Interferon {gamma}, a cytokine implicated in the vascular remodelling of the decidua necessary for embryo implantation, also increased the expression of HLA-G by DSC (P < 0.05).

CONCLUSIONS: Our results suggest the existence of a network in which hormones together with cytokines regulate the expression of HLA-G by DSC, and that may be of relevance in the maintenance of maternal–fetal tolerance.

Key words: decidual stromal cell/HLA-G/interferon {gamma}/interleukin-10/progesterone

Submitted on April 24, 2007; resubmitted on September 12, 2007; accepted on September 20, 2007.


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