First Author | Iwamura C | Year | 2017 |
Journal | Blood | Volume | 129 |
Issue | 2 | Pages | 171-176 |
PubMed ID | 27799160 | Mgi Jnum | J:238923 |
Mgi Id | MGI:5824591 | Doi | 10.1182/blood-2016-06-723742 |
Citation | Iwamura C, et al. (2017) Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis. Blood 129(2):171-176 |
abstractText | The microbiota is known to influence the generation of hematopoietic progenitors, although the pathways underlying this process are still poorly understood. NOD1 and NOD2 are intracellular sensors for both Gram-positive and Gram-negative bacteria, but their role in steady-state hematopoiesis has never been characterized. We observed that stimulation with NOD1 or NOD2 ligand had no effect on the survival/proliferation of hematopoietic precursors. Nonetheless, NOD1, but not NOD2, ligand induced expression of multiple hematopoietic cytokines (interleukin-7 [IL-7], Flt3L, stem cell factor [SCF], ThPO, and IL-6) from bone marrow mesenchymal stromal cells (MSCs) in vitro. Moreover, in vivo administration of NOD1 ligand to germ-free mice restored the numbers of hematopoietic stem cells and precursors in bone marrow as well as serum concentrations of IL-7, Flt3L, SCF, and ThPO to the levels displayed by specific pathogen-free control animals. Based on these findings, we propose that NOD1 signaling in MSCs serves as an important pathway underlying the requirement for microbiota in the maintenance of steady-state hematopoiesis. This function is distinct from that triggered by lipopolysaccharide in both its broad effects on multiple progenitors and specific targeting of MSCs as cytokine producing intermediates. |