Hassall’s Corpuscles as Dynamic and Functionally Specialized Structures

Hassall’s corpuscles were first described in 1846 by the British physician and anatomist Arthur Hill Hassall. During histological observations of the human thymus, he discovered distinctive concentric epithelial structures within the medulla, which he termed “Hassall’s corpuscles”. Hassall’s corpuscles are also called Hassall’s bodies. These structures share morphological and molecular features with the epidermis. Since Hassall’s corpuscles express late keratinization markers such as involucrin, keratin 10, and filaggrin, they are considered to be composed of terminally differentiated medullary thymic epithelial cells (mTECs). Recent fate-mapping and single-cell transcriptomic analyses have demonstrated that Hassall’s corpuscles originate from post-Aire mTECs, and their differentiation has been suggested to be Aire-dependent. Hassall’s corpuscles are now recognized as heterogeneous structures that play a role in central tolerance and regulatory T cell (Treg) development. In this review, we summarize recent advances in our understanding of the development of Hassall’s corpuscles within the mTEC lineage. We further describe that Hassall’s corpuscles undergo dynamic changes in size and number during thymic involution and regeneration. Thus, we propose that Hassall’s corpuscles should no longer be regarded as merely regressive structures but rather as functionally active bodies with critical immunological roles.