Immunomodulation par les molécules HLA-G solubles dans les syndromes lymphoprolifératifs et la GVHD aïgue : interaction avec des partenaires cellulaires de la réponse immunitaire
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Abstract EN:
Soluble HLA-G proteins are immunomodulatory molecules expressed in many pathological contexts. Here, we first found that functional soluble HLA-G plasmatic level was significantly increased for patients suffering of lymphoproliferative disorders, compared to healthy subjects. Then, a significant correlation was observed between low soluble HLA-G plasmatic level and Graft-versus-Host Disease occurrence for peripheral haematopoietic stem cells transplanted patients. Furthemore, soluble HLA-G molecules (i) seem to have a link with natural regulatory T lymphocytes ex vivo for transplanted patients and in vitro in mixed leukocyte reaction. And (ii) they display the capacity to inhibit activation of NK cells mediated by dendritic cells. So, these results strengthen the role of soluble HLA-G molecules in peripheral tolerance, their expression being (a) detrimental for cancer immunosurveillance and (b) advantageous against complications in allogeneic transplantation. Soluble HLA-G proteins are immunomodulatory molecules expressed in many pathological contexts. Here, we first found that functional soluble HLA-G plasmatic level was significantly increased for patients suffering of lymphoproliferative disorders, compared to healthy subjects. Then, a significant correlation was observed between low soluble HLA-G plasmatic level and Graft-versus-Host Disease occurrence for peripheral haematopoietic stem cells transplanted patients. Furthemore, soluble HLA-G molecules (i) seem to have a link with natural regulatory T lymphocytes ex vivo for transplanted patients and in vitro in mixed leukocyte reaction. And (ii) they display the capacity to inhibit activation of NK cells mediated by dendritic cells. So, these results strengthen the role of soluble HLA-G molecules in peripheral tolerance, their expression being (a) detrimental for cancer immunosurveillance and (b) advantageous against complications in allogeneic transplantation.
Abstract FR:
Lors de ce travail, l’expression et le potentiel immunomodulateur des molécules HLA-G solubles ont pu être mis en évidence dans deux types de contexte pathologique. Tout d’abord, des patients atteints de syndromes lymphoprolifératifs démontrent un taux plasmatique significativement élevé en molécules HLA-G solubles fonctionnelles, comparé à des sujets sains. Et, lors de la greffe de cellules souches hématopoïétiques du sang périphérique, un faible taux plasmatique en molécules HLA-G solubles est corrélé avec l’occurrence de la maladie du greffon contre l’hôte. Par la suite ont été constatés (i) un lien potentiel entre les molécules HLA-G solubles et les lymphocytes T régulateurs naturels, et (ii) une inhibition par HLA-G de la fonction activatrice des cellules dendritiques sur les NK. Ceci renforce l’implication de ces molécules (a) dans l’échappement des greffes à l’immunosurveillance et (b) dans la mise en place d’un environnement tolérogène bénéfique en transplantation.