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Division of Infection and Immunity

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Dr Jennifer Cowan

Sir Henry Dale Fellow

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Research in the Cowan lab focusses on T-cell development.

Research summary

T-cells play essential roles in immune responses. Antigen recognition by naive T-cells enables efficient responses against new immune challenges, and differentiation into long- term memory T-cells is the basis of vaccination. Dysregulated T-cell development results in diverse immunologically mediated diseases ranging from immunodeficiency to autoimmunity. Generation of T-cells occurs exclusively in the thymus, thus, this organ dictates the immunological competence of the host. However, T-cell development is not constant throughout life, and the thymus undergoes age-related involution that results in progressive deterioration of T-cell output, in addition to acute atrophy under multiple stressors such as infection, pregnancy, chemotherapy and malnutrition.

Age-associated loss of thymic function corresponds with alterations in T-cells observed with aging. These changes may underlie the loss of immunocompetence with age, however, this remains unknown because of limited models allowing efficient prevention or reversal of involution.  Changes in thymic size throughout life are controlled by thymic epithelial cells (TECs), including the decline in thymic tissue with age. The transcriptional assessment of TECs through development facilitated the generation of genetically altered mouse models in which thymic involution can be prevented or reversed.

The Cowan lab will use these newly generated models to establish the contribution thymic atrophy has on underlying age-related immune defects. We will explore if restoring thymic function alters peripheral T-cell populations and consequently T-cell responses of aging hosts when immune challenged. Moreover, the Cowan lab is interested in exploring the role of TECs in orchestrating this involution process. Our work aims to better understand the mechanisms underlying immune aging, so as to improve immune protection in aged individuals.

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