Cathepsin K maintains the compartment of bone marrow T lymphocytes in vivo

In this study, we investigated the influence of the loss of cathepsin K (Ctsk) gene on the hematopoietic system in vitro and in vivo. We found that cultures with lineage− SCA1+ KIT+ (LSK) cells onCtsk deficient stromal cells display reduced colony formation and proliferation, with increased differentiation, giving rise to repopulating cells with reduced ability to repopulate the donor LSKs and T cell compartments in the bone marrow (BM). Subsequent in vivo experiments showed impairment of lymphocyte numbers, but, gross effects on early hematopoiesis or myelopoiesis were not found. Most consistently in in vivo experimental settings, we found a significant reduction of (donor) T cell numbers in the BM. Lymphocyte deregulation is also found in transplantation experiments, which revealed thatCtsk is required for optimal regeneration of small populations of T cells, particularly in the BM, but also of thymic B cells. Interestingly, cell nonautonomousCtsk regulates both B and T cell numbers, but T cell numbers in the BM require an additional autonomousCtsk‐dependent process. Thus, we show thatCtsk is required for the maintenance of hematopoietic stem cells in vitro, but in vivo,Ctsk deficiency most strongly affects lymphocyte homeostasis, particularly of  T cells in the BM.
Source: Immunity, Inflammation and Disease - Category: Allergy & Immunology Authors: Tags: ORIGINAL RESEARCH Source Type: research