| First Author | Youm YH | Year | 2012 |
| Journal | Cell Rep | Volume | 1 |
| Issue | 1 | Pages | 56-68 |
| PubMed ID | 22832107 | Mgi Jnum | J:277584 |
| Mgi Id | MGI:6274074 | Doi | 10.1016/j.celrep.2011.11.005 |
| Citation | Youm YH, et al. (2012) The Nlrp3 inflammasome promotes age-related thymic demise and immunosenescence. Cell Rep 1(1):56-68 |
| abstractText | The collapse of thymic stromal cell microenvironment with age and resultant inability of the thymus to produce naive T cells contributes to lower immune-surveillance in the elderly. Here we show that age-related increase in 'lipotoxic danger signals' such as free cholesterol (FC) and ceramides, leads to thymic caspase-1 activation via the Nlrp3 inflammasome. Elimination of Nlrp3 and Asc, a critical adaptor required for inflammasome assembly, reduces age-related thymic atrophy and results in an increase in cortical thymic epithelial cells, T cell progenitors and maintenance of T cell repertoire diversity. Using a mouse model of irradiation and hematopoietic stem cell transplantation (HSCT), we show that deletion of the Nlrp3 inflammasome accelerates T cell reconstitution and immune recovery in middle-aged animals. Collectively, these data demonstrate that lowering inflammasome-dependent caspase-1 activation increases thymic lymphopoiesis and suggest that Nlrp3 inflammasome inhibitors may aid the re-establishment of a diverse T cell repertoire in middle-aged or elderly patients undergoing HSCT. |
