Bone marrow CX3CR1(+) mononuclear cells relay a systemic microbiota signal to control hematopoietic progenitors in mice

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The microbiota regulate hematopoiesis in the bone marrow (BM); however, the detailed mechanisms remain largely unknown. In this study, we explored how microbiota-derived molecules (MDMs) were transferred to the BM and sensed by the local immune cells to control hematopoiesis under steady-state conditions. We reveal that MDMs, including bacterial DNA (bDNA), reach the BM via systemic blood circulation and are captured by CX3CR1(+) mononuclear cells (MNCs). CX3CR1(+) MNCs sense MDMs via endolysosomal Toll-like receptors (TLRs) to produce inflammatory cytokines, which control the basal expansion of hematopoietic progenitors, but not hematopoietic stem cells, and their differentiation potential toward myeloid lineages. CX3CR1(+) MNCs colocate with hematopoietic progenitors at the perivascular region, and the depletion of CX3CR1(+) MNCs impedes bDNA influx into the BM. Moreover, the abrogation of TLR pathways in CX3CR1(+) MNCs abolished the microbiota effect on hematopoiesis. These studies demonstrate that systemic MDMs control BM hematopoiesis by producing CX3CR1(+) MNC-mediated cytokines in the steady-state.
Publisher
AMER SOC HEMATOLOGY
Issue Date
2019-10
Language
English
Article Type
Article
Citation

BLOOD, v.134, no.16, pp.1312 - 1322

ISSN
0006-4971
DOI
10.1182/blood.2019000495
URI
http://hdl.handle.net/10203/277050
Appears in Collection
MSE-Journal Papers(저널논문)
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