| First Author | Cheung K | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 43 | Pages | E5815-24 |
| PubMed ID | 26392551 | Mgi Jnum | J:227077 |
| Mgi Id | MGI:5699645 | Doi | 10.1073/pnas.1509627112 |
| Citation | Cheung K, et al. (2015) CD31 signals confer immune privilege to the vascular endothelium. Proc Natl Acad Sci U S A 112(43):E5815-24 |
| abstractText | Constitutive resistance to cell death induced by inflammatory stimuli activating the extrinsic pathway of apoptosis is a key feature of vascular endothelial cells (ECs). Although this property is central to the maintenance of the endothelial barrier during inflammation, the molecular mechanisms of EC protection from cell-extrinsic, proapoptotic stimuli have not been investigated. We show that the Ig-family member CD31, which is expressed by endothelial but not epithelial cells, is necessary to prevent EC death induced by TNF-alpha and cytotoxic T lymphocytes in vitro. Combined quantitative RT-PCR array and biochemical analysis show that, upon the engagement of the TNF receptor with TNF-alpha on ECs, CD31 becomes activated and, in turn, counteracts the proapoptotic transcriptional program induced by TNF-alpha via activation of the Erk/Akt pathway. Specifically, Akt activation by CD31 signals prevents the localization of the forkhead transcription factor FoxO3 to the nucleus, thus inhibiting transcription of the proapoptotic genes CD95/Fas and caspase 7 and de-repressing the expression of the antiapoptotic gene cFlar. Both CD31 intracellular immunoreceptor tyrosine-based inhibition motifs are required for its prosurvival function. In vivo, CD31 gene transfer is sufficient to recapitulate the cytoprotective mechanisms in CD31(-) pancreatic beta cells, which become resistant to immune-mediated rejection when grafted in fully allogeneic recipients. |
