Knock-down of HEXA and HEXB genes correlate with the absence of the immunostimulatory function of HSC-derived dendritic cells
✍ Scribed by Roberto Tiribuzi; Francesco D'Angelo; Anna C. Berardi; Sabata Martino; Aldo Orlacchio
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 298 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0263-6484
- DOI
- 10.1002/cbf.1819
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✦ Synopsis
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. Copyright © 2011 John Wiley & Sons, Ltd.