Sepsis-Induced Thymic Atrophy Is Associated with Defects in Early Lymphopoiesis
| Autor: | René Winkler, Yu Zhang, Tao Lin, Beibei Wang, Peng Miao, Junyan Han, Hui Zeng, Yajie Li, Yu Zhou, Christian Kosan, Yaxian Kong, Jianping Zhang, Ulrike Kröhnert, Zhengya Yu, Shaoxin Yuan, Weimei Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine T-Lymphocytes Bone Marrow Cells Thymus Gland Biology 03 medical and health sciences Sepsis medicine Animals Cell Lineage Lymphocyte Count Lymphopoiesis Progenitor cell Cell Proliferation Myelopoiesis Gene Expression Profiling Toll-Like Receptors Cell Biology Hematopoietic Stem Cells Acquired immune system Mice Inbred C57BL Haematopoiesis Poly I-C 030104 developmental biology medicine.anatomical_structure Hematopoiesis Extramedullary Immunology Molecular Medicine Receptors Chemokine Bone marrow Atrophy Stem cell CC chemokine receptors Developmental Biology Homing (hematopoietic) |
| Zdroj: | Stem Cells. 34:2902-2915 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.2464 |
| Popis: | Impaired T lymphopoiesis is associated with immunosuppression of the adaptive immune response and plays a role in the morbidity and mortality of patients and animal models of sepsis. Although previous studies examined several intrathymic mechanisms that negatively affect T lymphopoiesis, the extrathymic mechanisms remain poorly understood. Here, we report a dramatic decrease in the percentage of early T lineage progenitors (ETPs) in three models of sepsis in mice (cecal ligation and puncture, lipopolysaccharide continuous injection, and poly I:C continuous injection). However, septic mice did not show a decrease in the number of bone marrow (BM) precursor cells. Instead, the BM progenitors for ETPs expressed reduced mRNA levels of CC chemokine receptor (CCR) 7, CCR9 and P-selectin glycoprotein ligand 1, and exhibited impaired homing capacity in vitro and in vivo. Furthermore, RNA-Seq analysis and real-time PCR showed a marked downregulation of several lymphoid-related genes in hematopoietic stem and progenitor cells. Hematopoietic stem and progenitor cells differentiated into myeloid cells but failed to generate T lymphocytes in vitro and in vivo. Our results indicate that the depletion of ETPs in septic mice might be a consequence of an impaired migration of BM progenitors to the thymus, as well as a defect in lymphoid lineage commitment. |
| Databáze: | OpenAIRE |
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