Sepsis-induced thymic atrophy is associated with defects in early lymphopoiesis
Y Kong, Y Li, W Zhang, S Yuan, R Winkler… - Stem Cells, 2016 - academic.oup.com
Y Kong, Y Li, W Zhang, S Yuan, R Winkler, U Kröhnert, J Han, T Lin, Y Zhou, P Miao…
Stem Cells, 2016•academic.oup.comImpaired 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 …
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 …
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.
Oxford University Press