Cell‐type‐specific role of lamin‐B1 in thymus development and its inflammation‐driven reduction in thymus aging

• Published in: Aging cell 2019-08, Vol.18 (4), p.e12952-n/a
• Main Authors: Yue, Sibiao, Zheng, Xiaobin, Zheng, Yixian
• Format: Article
• Language: English
• Subjects: Aging; Animals; Architecture; Cell Differentiation - genetics; Cytokines; Cytokines - metabolism; Degeneration; Developmental biology; Epithelial cells; Epithelial Cells - metabolism; Female; Gene Expression Regulation, Developmental - genetics; Immunosenescence - genetics; Inflammation; Inflammation - metabolism; Lamin Type B - genetics; Lamin Type B - metabolism; lamin-B1; Lamins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neomycin; Organogenesis; Organogenesis - genetics; Organogenesis - immunology; Original; Proteins; Ribonucleic acid; RNA; Senescence; Structural proteins; Thymus; Thymus Gland - cytology; Thymus Gland - growth & development; thymus involution; Up-Regulation - genetics
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.12952

Cellular architectural proteins often participate in organ development and maintenance. Although functional decay of some of these proteins during aging is known, the cell‐type‐specific developmental role and the cause and consequence of their subsequent decay remain to be established especially in mammals. By studying lamins, the nuclear structural proteins, we demonstrate that lamin‐B1 functions specifically in the thymic epithelial cells (TECs) for proper thymus organogenesis. An up‐regulation of proinflammatory cytokines in the intra‐thymic myeloid immune cells during aging accompanies a gradual reduction of lamin‐B1 in adult TECs. We show that these cytokines can cause senescence and lamin‐B1 reduction of the young adult TECs. Lamin‐B1 supports the expression of TEC genes that can help maintain the adult TEC subtypes we identified by single‐cell RNA‐sequencing, thymic architecture, and function. Thus, structural proteins involved in organ building and maintenance can undergo inflammation‐driven decay which can in turn contribute to age‐associated organ degeneration. Lamin‐B1 supports thymic organogenesis and function in thymic epithelial cells (TECs). Age‐associated thymic inflammation accompanies lamin‐B1 reduction in TECs. Inflammatory cytokines in thymus trigger postnatal TEC senescence and lamin‐B1 reduction. TEC lamin‐B1 maintains the composition of adult TEC subsets, thymic structure, and function.