Immunology

Tumor suppressor is a thymic booster

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Science  25 Aug 2017:
Vol. 357, Issue 6353, pp. 769-770
DOI: 10.1126/science.357.6353.769-f

Thymic epithelial cells (TECs) choreograph the development of functional self-tolerant T cells. However, factors such as aging and chemotherapy can lead to TEC dysfunction, resulting in autoimmunity and impaired immunosurveillance. Rodrigues et al. conditionally deleted the tumor suppressor protein p53 in TECs and found that their numbers were reduced in the medulla, although cortical TEC organization and T cell development in early life were normal. Yet with age, these defects spread to the cortex. Likewise, thymic involution and hallmarks of peripheral autoimmune disease were enhanced. p53 appears to fine-tune RANK, a known mediator of TEC function, but RNA sequencing suggests that other pathways may be important. These findings increase our understanding of how p53 regulates immune homeostasis, but also suggest caution in the use of p53 inhibitors to lessen side effects in chemotherapy.

Blood 130, 4 (2017).

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