GSE192363
The TAM receptor tyrosine kinases Axl and Mer drive the phagocytic differentiation of tissue-resident macrophages
Many apoptotic thymocytes are generated during the course of T cell selection in the thymus, yet the machinery through which these dead cells are recognized and phagocytically cleared is incompletely understood. We find that the TAM receptor tyrosine kinases Axl and Mer, which are co-expressed by a specialized set of phagocytic thymic macrophages, are essential components of this machinery. Axl-/-Mertk-/- double mutant mice exhibited a marked accumulation of apoptotic cells during the time that autoreactive and nonreactive thymocytes die. Unexpectedly, the double mutants also displayed a profound deficit in the total number of phagocytic macrophages in the thymus, and concomitantly exhibited diminished expression of key non-TAM engulfment systems in the macrophages that remain. These previously unrecognized deficits were not confined to the thymus, and were also evident in the bone marrow and spleen. They had pleiotropic metabolic consequences for the double mutants, which included severe dysregulation of hemoglobin turnover, iron metabolism, and erythropoiesis. Overall design: stranded mRNA sequencing