Dynamics of the Neonatal Thymic Microenvironment Maintain Peripheral Regulatory T Cells and Influence the Onset of Autoimmunity
Neonatal thymectomy (TX) has been known to induce experimental autoimmune disease models in mice for over half a century. The thymic microenvironment, including thymic epithelial cells (TECs), plays a crucial role in establishing self-tolerance in T cells. However, the extent to which the dynamic changes in the neonatal thymic environment contribute to the onset of autoimmunity remains incompletely understood. In this study, we analyzed the detailed alterations in the neonatal thymus and peripheral lymphoid organs using a mouse model of primary SjÃ¶gren disease (pSjD). Mice treated with TX at 3 days after birth (day 3-TX) exhibited significantly more severe autoimmune pathology than those in day 7-TX mice. Around day 3, T cell differentiation and the expansion of TECs, particularly medullary TECs (mTECs), were markedly accelerated in the neonatal thymus. Furthermore, in day 3-TX mice, the expansion of peripherally induced regulatory T cells (pTreg) was impaired, along with the loss of thymic-derived Treg (tTreg) cell output. These findings suggest that the neonatal thymic environment plays a critical role in regulating peripheral immune tolerance and may influence the pathogenesis of autoimmune diseases.