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- Morandi, F, et al.
(författare)
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Human Amnion Epithelial Cells Impair T Cell Proliferation: The Role of HLA-G and HLA-E Molecules
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- The immunoprivilege status characteristic of human amnion epithelial cells (hAECs) has been recently highlighted in the context of xenogenic transplantation. However, the mechanism(s) involved in such regulatory functions have been so far only partially been clarified. Here, we have analyzed the expression of HLA-Ib molecules in isolated hAEC obtained from full term placentae. Moreover, we asked whether these molecules are involved in the immunoregulatory functions of hAEC. Human amnion-derived cells expressed surface HLA-G and HLA-F at high levels, whereas the commonly expressed HLA-E molecule has been measured at a very low level or null on freshly isolated cells. HLA-Ib molecules can be expressed as membrane-bound and soluble forms, and in all hAEC batches analyzed we measured high levels of sHLA-G and sHLA-E when hAEC were maintained in culture, and such a release was time-dependent. Moreover, HLA-G was present in extracellular vesicles (EVs) released by hAEC. hAEC suppressed T cell proliferation in vitro at different hAEC:T cell ratios, as previously reported. Moreover, inhibition of T cell proliferation was partially reverted by pretreating hAEC with anti-HLA-G, anti-HLA-E and anti-β2 microglobulin, thus suggesting that HLA-G and -E molecules are involved in hAEC-mediated suppression of T cell proliferation. Finally, either large-size EV (lsEV) or small-size EV (ssEV) derived from hAEC significantly modulated T-cell proliferation. In conclusion, we have here characterized one of the mechanism(s) underlying immunomodulatory functions of hAEC, related to the expression and release of HLA-Ib molecules.
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- Sadeghi, L, et al.
(författare)
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Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between lymphoma cells and stromal cells play a key role in promoting tumor survival and development of drug resistance. We identified differences in key signaling pathways between the JeKo-1 and REC-1 mantle cell lymphoma (MCL) cell lines, displaying different patterns of stromal cell adhesion and chemotaxis towards stroma-conditioned medium. The identified adhesion-regulated genes reciprocated important aspects of microenvironment-mediated gene modulation in MCL patients. Five-hundred and ninety genes were differently regulated between the cell lines upon adhesion to stromal cells, while 32 genes were similarly regulated in both cell lines. Regulation of B-cell Receptor (BCR) signature genes in adherent cells was specific for JeKo-1. Inhibition of BCR using siRNA or clinically approved inhibitors, Ibrutinib and Acalabrutinib, decreased adhesion of JeKo-1, but not REC-1 cells. Cell surface levels of chemokine receptor CXCR4 were higher in JeKo-1, facilitating migration and adhesion of JeKo-1 but not REC-1 cells. Surface levels of ICAM1 adhesion protein differ for REC-1 and JeKo-1. While ICAM1 played a positive role in adherence of both cell lines to stromal cells, S1PR1 had an inhibitory effect. Our results provide a model framework for further investigation of mechanistic differences in patient-response to new pathway-specific drugs.
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