Modern view on the function of Hassall’s corpuscles

Hassall’s corpuscles are unique epithelial structures of the thymus medulla. Despite the long history of thymic corpuscle research, their functions and structural features still require further study. This review analyzes modern literature data on the structure, origin, and functional role of Hassall’s corpuscles in health and various pathologies. It is shown that the main structural component of the corpuscles are medullary thymic epithelial cells (mTEC) at the terminal stages of differentiation, which undergo keratinization similar to epidermal cells. In addition to mTEC, the bodies include microenvironment cells: dendritic cells, macrophages, myoid cells, and lymphocytes. Modern studies using single-cell RNA sequencing and spatial transcriptomics have shown that «aging» mTEC of Hassall’s corpuscles produce a wide range of cytokines, chemokines, and antimicrobial peptides, forming a specific proinflammatory microenvironment of the thymus medulla. The interaction of secreted factors with cells of innate and adaptive immunity plays an important role in the processes of negative selection of autoreactive thymocytes and differentiation of regulatory T-lymphocytes. Structural and functional changes in Hassall’s corpuscles observed in age-related thymus involution and various pathological conditions can lead to a violation of central immunological tolerance and the development of autoimmune diseases. Thus, Hassall’s corpuscles are not only morphological markers of thymus involution, but also functionally active structures involved in maintaining thymic homeostasis. Further studies of the molecular mechanisms that control the morphogenesis and activity of Hassall’s corpuscles may open up new possibilities for developing approaches to correcting age-related changes in the immune system.