Mechanisms of regulation of HLA-G molecule expression
The group investigates the mechanisms involved in the control of HLA-G expression, a molecule originally identified in the placenta and involved in immune tolerance. The long-term goal is to downregulate HLA-G expression in cancer and infectious diseases and upregulate it in transplantation.
The group evidenced that HLA-G expression is controlled at the transcriptional level by a unique gene promoter when compared with classical HLA-class I genes, and at the post-transcriptional level including alternative splicing, mRNA stability, translation and protein transport to the cell surface. To identify key mechanisms involved in the regulation of HLA-G expression four complementary aspects are studied: (i) the influence of epigenetic mechanisms, (ii) the identification of transcriptional machinery (iii) the modulation of expression by microenvironmental agents and (iv) the impact of gene polymorphism.
The team is coordinating Franco-Brazilian projects (CAPES-COFECUB, Ciênca sem fronteiras programs and ANRS) whose lab partner located in the Faculty of Medicine of Ribeirão Preto is attached to the University of São Paulo.
Main contributions :
- Identification of microenvironmental factors and target sites involved in the regulation of HLA-G expression (IL-10, TNF-alpha, interferons, glucocorticoids, hypoxia) .
- Characterization of the mechanisms of HLA-G repression: DNA methylation, histone modifications and RREB1 factor in vitro et in vivo.
- Demonstration of the impact of polymorphisms of the 5 'and 3' untranslated regions on the HLA-G gene expression.
- Identification of new HLA-G alleles and alleles associated with pre-eclampsia and malaria.
- Multicentric study on the expression of HLA-G in glioblastoma and its impact on patient survival.