Metabolic regulation of thymic stromal cell function

By mining stromal datasets, we found that thymic stromal cells naturally express very low levels of the hydrogen peroxide-quenching enzyme Catalase. Since Catalase is generally expressed in most other cell types, we wondered what the selective advantage could be for establishing a highly oxidative environment in thymic stromal cells. Hydrogen peroxide is a second messenger involved in many cellular process, and Manpreet’s dissertation work revealed that one function of high hydrogen peroxide levels in stromal cells is to drive high levels of basal autophagy, which is critical for self-antigen presentation and tolerance induction in developing T cells. We are investigating how the redox status of stromal cells is maintained, and how it regulates their function.

Paper links: Semwal 2021 (review), Semwal 2022, Hester 2022

Current funding: R21AI48522, R21AI154109

Past funding: R01AI121367, R56AI153626

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Age-associated thymus dysfunction