Thymic macrophage restoration after depletion relies on self-proliferation and Ly6C+ monocytes recruitment 4716

Abstract Description Thymic macrophages consist of two populations distinguished by the expression of Timd4 and Cx3cr1. Timd4+ cells are located in the cortex, while Cx3cr1+ macrophages are restricted to the medulla and the cortico-medullary junction. The two populations have distinct origins. Timd4+ thymic macrophages are of embryonic origin, while Cx3cr1+macrophages are derived from adult hematopoietic stem cells. To understand how thymic macrophages are restored after acute injury, we used a diphtheria toxin-based depletion system combined with non-genotoxic bone marrow chimeras. Increased proliferation and influx of hematopoietic stem cell-derived cells contributed to the replacement of both populations of thymic macrophages. The proliferation of Timd4+ cells and the recruitment of circulating progenitors among them were limited compared to Cx3cr1+ cells, explaining the reduction of their numbers and proportions after the recovery. Ccr2-deficient bone marrow was severely impaired in its ability to replace thymic macrophages in mixed bone marrow chimera, pointing to the critical role of monocytes in the process. However, the contribution of Cx3cr1-/-progenitors was on par with wild-type competitors, ruling out the participation of LyC6- patrolling monocytes. Thus, we conclude that LyC6+ classical monocytes recruitment from the blood and the proliferation of surviving cells play critical roles in restoring thymic macrophages after acute injury. Funding Sources NSTC (Taiwan) grant 111-2320-B-A49-031-MY3, NYCU Cancer and Immunology Research Center, Disease Prevention Center Topic Categories Hematopoiesis and Immune System Development (HEM)