Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells
نویسندگان
چکیده
OBJECTIVE Interleukin (IL)-7 is mainly produced in bone marrow (BM) that forms the niche for B cells. We previously demonstrated that BM also retains pathogenic memory CD4 T cells in murine models of inflammatory bowel disease (IBD). However, it remains unknown whether BM-derived IL-7 is sufficient for the development of IBD and which cells form the niche for colitogenic memory CD4 T cells in BM. DESIGN To address these questions, we developed mice in which IL-7 expression was specific for BM, and identified colitis-associated IL-7-expressing mesenchymal stem cells (MSC) in the BM. RESULTS IL-7-/-×RAG-1-/- mice injected with BM cells from IL-7+/+×RAG-1-/- mice, but not from IL-7-/-×RAG-1-/- mice, expressed IL-7 in BM, but not in their colon, and developed colitis when injected with CD4+CD45RBhigh T cells. Cultured BM MSC stably expressed a higher level of IL-7 than that of primary BM cells. IL-7-sufficient, but not IL-7-deficient, BM MSC supported upregulation of Bcl-2 in, and homeostatic proliferation of, colitogenic memory CD4 T cells in vitro. Notably, IL-7-/-×RAG-1-/- mice transplanted with IL-7-sufficient, but not IL-7-deficient, BM MSC expressed IL-7 in BM, but not in their colon, and developed colitis when transplanted with CD4+CD45RBhigh T cells. CONCLUSIONS We demonstrate for the first time that BM MSC are a major source of IL-7 and play a pathological role in IBD by forming the niche for colitogenic CD4 memory T cells in BM.
منابع مشابه
Bone marrow mesenchymal stem cells are major source of IL-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells
متن کامل
Mild hypoxia and human bone marrow mesenchymal stem cells synergistically enhance expansion and homing capacity of human cord blood CD34+ stem cells
Objective(s): Cord blood (CB) is known as a valuable source of hematopoietic stem cells (HSC). Identifying strategies that enhance expansion and maintain engraftment and homing capacity of HSCs can improve transplant efficiency. In this study, we examined different culture conditions on ex vivo expansion and homing capacity of CB-HSCs. Materials and Methods: In this study, 4-5 different units o...
متن کاملتاثیر آشیانههای جفتی شبیهسازی شده با داربست پلی لاکتیک اسید در تکثیر سلولهای بنیادی خونساز مشتق از بافت جفت انسانی
Background and Objective: Nowadays, although umbilical cord blood is a commonly used source of hematopoietic stem cell, its low frequency of these cells is the main factor limiting its clinical application. The transplantation of hematopoietic stem cells derived from placenta tissue along with umbilical cord blood cells of the same sample may be an appropriate approach to solve this problem. In...
متن کاملEvaluation of Therapeutic Effects of Autologous Bone Marrow Mesenchymal Stem Cells to Prevent the Progression of Chronic Nephropathy in Renal Transplant
Background Chronic allograft nephropathy(CAN) is one of the most common causes of chronic and end stage renal disease. It is defined with Mainly tubular atrophy and interstitial fibrosis and no evidence of any other etiology, or functional disorder that caused at least three months after transplantation . Control of risk factors (HTN,DM,HLP, …) and limiting usage of calcineurin inhibitors...
متن کاملComparative Analysis of Mesenchymal Stem Cells Isolated from Human Bone Marrow and Wharton’s Jelly
Introduction: Bone marrow (BM) is a known source of mesenchymal stem cells (MSCs) that are used for cell therapy. This study attempts to identify if the Wharton’s Jelly (WJ) is a suitable substitute for BM as a source for MSCs. Materials and Methods: A population of human WJ and BM stem cells were isolated and incubated with fluorescein conjugated antibodies for five specific MSC markers....
متن کامل