The role of autophagy in thymic stromal cell maintenance with age

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Abstract T lymphocytes develop in the thymus, where mutually inductive signaling between lymphoid progenitors and thymic stromal cells (TSCs) directs the progenitors along a well-characterized program of differentiation. However, the biology of the TSCs comprising the lymphopoietic thymic microenvironment remains relatively under-characterized because stromal cells are rare and difficult to isolate. TSCs exhibit high basal levels of autophagy at the steady state, which is critical for self-antigen presentation and T cell selection. The mechanisms governing high basal autophagy in TSCs are unknown, however autophagy is induced by many stressors, including high H202 levels. Using a deconvolution technique to study gene expression essentially in situ, we previously identified a deficiency in the H202 quenching enzyme catalase (CAT) in TSCs, and found that CAT deficiency results in high H202 levels in this population, eventually leading to thymic atrophy. Our current studies address the possibility that, in addition to a role in self-antigen presentation, autophagy may also mitigate thymic atrophy through its role in removing organelle damaged by H202. Our preliminary studies suggest that increased basal autophagy in Beclin 1 knock-in (Becn1F121A/F121A) mice promotes thymus function during aging. Supported by N.I.H. grant R01AI121367

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