This study suggests that activation of the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome contributes to thymic involution and decreases thymic export of naive T cells in aged individuals. The authors found that myeloid cells in the mouse thymus showed an age-dependent progressive increase in the activation of caspase 1. Aged mice had higher levels of free cholesterol and ceramides, and these age-related 'danger' signals could promote caspase 1 activation in macrophages. Notably, age-related caspase 1 activation and thymic involution was reduced in mice deficient in the inflammasome components NLRP3 and ASC. Furthermore, aged NLRP3- or ASC-deficient mice had increased numbers of cortical epithelial cells and T cell progenitors and a more diverse peripheral T cell repertoire compared with wild-type controls. Aged NLRP3-deficient mice also showed increased T cell reconstitution in a model of haematopoietic stem cell transplantation. The authors suggest that pharmacological inhibition of the inflammasome could boost immune function in elderly patients.
ORIGINAL RESEARCH PAPER
Youm, Y.-H. et al. The NLRP3 inflammasome promotes age-related thymic demise and immunosenescence. Cell Rep. 1, 56–68 (2012)Article
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Bordon, Y. Inflammasome blockade keeps the thymus young. Nat Rev Immunol 12, 154 (2012). https://doi.org/10.1038/nri3188
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DOI: https://doi.org/10.1038/nri3188