IL-6 Generated from Human Hematopoietic Stem and Progenitor Cells through TLR4 Signaling Promotes Emergency Granulopoiesis by Regulating Transcription Factor Expression
| Autor: | Isuzu Kobayashi, Tatsufumi Goto, Hideki Wakui, Kumi Ubukawa, Ken Asanuma, Yumi Sasaki, Naoto Takahashi, Yong-Mei Guo, Kenichi Sawada |
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| Rok vydání: | 2021 |
| Předmět: |
Immunology
CD34 Antigens CD34 Granulocyte Biology Granulopoiesis Monocytes Bone Marrow medicine Humans Immunology and Allergy Granulocyte Precursor Cells Progenitor cell Autocrine signalling Myelopoiesis Interleukin-6 CCAAT-Enhancer-Binding Protein-beta Stem Cells Hematopoietic Stem Cell Transplantation Cell Differentiation Hematopoietic Stem Cells Adaptation Physiological Cell biology Toll-Like Receptor 4 Haematopoiesis medicine.anatomical_structure Gene Expression Regulation Cytokines Bone marrow Granulocytes Signal Transduction |
| Zdroj: | The Journal of Immunology. 207:1078-1086 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2100168 |
| Popis: | Emergency granulopoiesis, also known as demand-adapted granulopoiesis, is defined as the response of an organism to systemic bacterial infections, and it results in neutrophil mobilization from reservoir pools and increased myelopoiesis in the bone marrow. Indirect and direct initiating mechanisms of emergency granulopoiesis have been hypothesized. However, the detailed mechanism of hyperactive myelopoiesis in the bone marrow, which leads to granulocyte left shift, remains unknown. In this study, we report that TLR4 is expressed on granulo-monocytic progenitors, as well as mobilized human peripheral blood CD34+ cells, which account for 0.2% of monocytes in peripheral blood, and ∼ 10% in bone marrow. LPS, a component of Gram-negative bacteria that results in a systemic bacterial infection, induces the differentiation of peripheral blood CD34+ cells into myelocytes and monocytes in vitro via the TLR4 signaling pathway. Moreover, CD34+ cells directly responded to LPS stimulation by activating the MAPK and NF-κB signaling pathways, and they produced IL-6 that promotes emergency granulopoiesis by phosphorylating C/EBPα and C/EBPβ, and this effect was suppressed by the action of an IL-6 receptor inhibitor. This work supports the finding that TLR is expressed on human hematopoietic stem and progenitor cells, and it provides evidence that human hematopoietic stem and progenitor cells can directly sense pathogens and produce cytokines exerting autocrine and/or paracrine effects, thereby promoting differentiation. |
| Databáze: | OpenAIRE |
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