Work

Topoisomerase 1 is required for the development and function of thymus 3431

Year: 2025

Type: article

Abstract: Description Thymus organogenesis is critical for the proper maturation of developing T cells. In this study, we identified Topoisomerase 1 (Top1) as a novel gene involved in thymus development and function. We created a mouse line with deletion of Top1 in thymic epithelial cells (TECs) and our results demonstrate that biallelic loss of Top1 in TECs causes congenital thymic aplasia, precipitating T cell immunodeficiency. Transcriptomic analysis provides insights into the molecular mechanism of Top1 in thymus development as we identify key genes involved in thymus organogenesis as the transcriptional targets of Top1 in TECs. Analysis of peripheral immunological compartments revealed severe loss of ab T cells complemented with a disproportionate accumulation of gd T cells and myeloid cells upon deletion of Top1 in TECs. The residual ab T cells in Top1 knock-out mice were effector and oligoclonal in nature, highlighting their self-reactivity. These results reveal a previously unknown role of Top1 in thymus development and T cell homeostasis. We propose Top1 as a genetic target for altered thymic development and T cell lymphopenia. Topic Categories Hematopoiesis and Immune System Development (HEM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1239

Author: Amit Kumar

Institution: Jawaharlal Nehru Centre for Advanced Scientific Research

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze