CXCL12-abundant Reticular Cells are the Major Source of IL-6 Upon LPS-stimulation and Thereby Regulate Hematopoiesis
Research output: Contribution to journal › Journal article › Research › peer-review
Hematopoiesis is maintained by hematopoietic stem and progenitor cells (HSPCs) that are located in the bone marrow (BM) where they are embedded within a complex supportive microenvironment, consisting of a multitude of various non-hematopoietic and hematopoietic cell types. The BM microenvironment not only regulates steady-state hematopoiesis by provision of growth factors, cytokines and cell-cell contact but is also an emerging key player during the adaptation to infectious and inflammatory insults (emergency hematopoiesis). Through a combination of gene expression analyses in prospectively isolated non-hematopoietic BM cell populations and various mouse models we have revealed that BM CXCL12-abundant reticular (CAR) cells are a major source of systemic and local BM IL-6 levels during emergency hematopoiesis following lipopolysaccharide (LPS) stimulation. Importantly, while IL-6 is dispensable during the initial phase of LPS-induced emergency hematopoiesis, it is required to sustain an adequate hematopoietic output during chronic-repetitive inflammation. Our data highlight the essential role of the non-hematopoietic BM microenvironment for the sensing and integration of pathogen-derived signals into sustained demand-adapted hematopoietic responses.</jats:p>
Original language | English |
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Journal | Blood advances |
Volume | 5 |
Issue number | 23 |
Pages (from-to) | 5002-5015 |
ISSN | 2473-9529 |
DOIs | |
Publication status | Published - 2021 |
Externally published | Yes |
ID: 328531037