title: Knock-down of HEXA and HEXB genes correlate with the absence of the immunostimulatory function of HSC-derived dendritic cells.
abstract: In an attempt to investigate whether the genetic defect in the HEXA and HEXB genes (which causes the absence of the lysosomal β-N-acetyl-hexosaminidase), are related to the wide inflammation in GM2 gangliosidoses (Tay-Sachs and Sandhoff disease), we have chosen the dendritic cells (DCs) as a study model. Using the RNA interference approach, we generated an in vitro model of HEXs knock-down immunogenic DCs (i-DCs) from CD34(+)-haemopoietic stem cells (CD34(+)-HSCs), thus mimicking the Tay-Sachs (HEXA-/-) and Sandhoff (HEXB-/-) cells. We showed that the absence of β-N-acetyl-hexosaminidase activity does not alter the differentiation of i-DCs from HSCs, but it is critical for the activation of CD4(+)T cells because knock-down of HEXA or HEXB gene causes a loss of function of i-DCs. Notably, the silencing of the HEXA gene had a stronger immune inhibitory effect, thereby indicating a major involvement of β-N-acetyl-hexosaminidase A isoenzyme within this mechanism.
authors: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors: Roberto
authors: R
authors: Tiribuzi
authors: Francesco
authors: F
authors: D'Angelo
authors: Anna C
authors: AC
authors: Berardi
authors: Sabata
authors: S
authors: Martino
authors: Aldo
authors: A
authors: Orlacchio
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020143:Gangliosidoses, GM2 / Q000276:immunology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D054820:beta-Hexosaminidase alpha Chain / Q000235:genetics* / Q000378:metabolism; D054821:beta-Hexosaminidase beta Chain / Q000235:genetics* / Q000378:metabolism
chemical_list: C518253:HEXA protein, human; C513386:HEXB protein, human; D054820:beta-Hexosaminidase alpha Chain; D054821:beta-Hexosaminidase beta Chain