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- W4313373787 abstract "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. 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 high H202 levels serve physiological functions in TSCs in the young, steady state thymus. 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. Our data indicate that catalase overexpression targeted to mitochondria in transgenic mice (mCAT Tg) results in diminished autophagy in TSCs and causes diminished negative selection in the thymus, eventually leading to autoimmunity. The effects on negative selection in mCAT Tg mice are rescued by increased basal autophagy on the beclin 1 knock-in (Becn1F121A/F121A) background. Our results suggest that the high basal autophagy level required in TSCs for T cell negative selection is promoted by physiologically low levels of catalase expression in the steady state thymus." @default.
- W4313373787 created "2023-01-06" @default.
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- W4313373787 date "2020-05-01" @default.
- W4313373787 modified "2023-10-06" @default.
- W4313373787 title "Redox regulation of autophagy in thymic stromal cell function" @default.
- W4313373787 doi "https://doi.org/10.4049/jimmunol.204.supp.62.7" @default.
- W4313373787 hasPublicationYear "2020" @default.
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