Sepsis-Induced Thymic Atrophy Is Associated with Defects in Early Lymphopoiesis. (1st August 2016)

• Record Type: Journal Article
• Authors: Kong, Yaxian; Li, Yajie; Zhang, Weimei; Yuan, Shaoxin; Winkler, René; Kröhnert, Ulrike; Han, Junyan; Lin, Tao; Zhou, Yu; Miao, Peng; Wang, Beibei; Zhang, Jianping; Yu, Zhengya; Zhang, Yu; Kosan, Christian; Zeng, Hui
• Is Part Of: Stem cells. Volume 34:Number 12(2016:Dec.)
• Page Start: 2902
• Page End: 2915
• Publication Date: 2016-08-01
• Subjects: Hematopoietic stem cells -- Emergency hematopoiesis -- Sepsis -- T lymphopoiesis -- Lineage commitment -- Thymic atrophy; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2464
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: 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. Abstract : A dramatic decrease of early T lineage progenitors (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 accompanied by enhanced myelopoiesis, suggesting a novel view of how sepsis induces lymphopenia.