Thymic innate lymphoid cells promote thymocyte differentiation of transplanted hematopoietic progenitors in immunodeficient mice.

Abstract Patients with combined immunodeficiencies can be cured by intravenous transfer of allogeneic hematopoietic stem and progenitor cells (HSPC). However, complications such as an impaired delayed T cell differentiation are unfortunately common, notably due to the defective thymic architecture in these patients requirement HSPC homing thymus. To circumvent problems, we have developed innovative approach based on direct targeting into thymus intrathymic (IT) injection. Using ZAP70-deficient mice a paradigm, previously showed that IT injection support long-term thymus-autonomous differentiation. Here, show WT results rapid engraftment Donor-derived thymocytes expand >100-fold, accounting for >13% cellularity 3 weeks post importantly, occurs absence cytoreductive conditioning. While mature CD4 thymocyte weeks, Treg requires 4 weeks. The kinetics development parallels generation medulla, appearance medullary epithelial at 3–4 transplantation. Notably, medulla is associated donor-derived RORγT+ innate lymphoid (ILC). ILC not required physiological thymopoiesis, find they critical presenting medulla. These may open new therapeutic avenues, promoting via IT-mediated transfer, enhancing Supported grants from ANR (CHIC) AFM-Telethon