Andri Leó Lemarquis

T cells are essential regulators of immunity, protecting against infections, autoimmunity, and cancer. Their production relies on a functional thymus, which is highly susceptible to damage from cancer therapies. Unfortunately, thymic recovery is incomplete in many cancer patients, and strategies to enhance immune regeneration are needed. My research focuses on the role of recirculating regulatory T cells (Tregs) in this process. I recently discovered that this population promotes thymic epithelial cell regeneration via Amphiregulin. Using machine learning approaches, I discovered that these Tregs express also Trefoil Factor 1 (TFF1) and the RNA-binding protein ZFP36L1, both implicated in tissue repair and Treg stability. This project aims to dissect the mechanistic roles of these factors in thymic regeneration. In Aim 1, I propose to investigate how Treg-derived TFF1 promotes thymic epithelial cell  regeneration. In Aim 2, I propose to study how ZFP36L1 stabilizes Tregs after injury. In Aim 3, I propse to analyse a recently generated atlas of thymic regeneration in human thymic samples to map regenerative pathways from thymic Tregs using spatial transcriptomics on human thymic samples from pediatric, aging, and post-chemotherapy patients. By integrating these approaches, I aim to define novel pathways for thymic regeneration, informing new strategies to improve immune recovery in cancer patients and aging individuals.