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Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis.

Abstract：

: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.

journal_name

Blood

journal_title

Blood

authors

Iwamura C,Bouladoux N,Belkaid Y,Sher A,Jankovic D

doi

10.1182/blood-2016-06-723742

subject

Has Abstract

pub_date

2017-01-12 00:00:00

pages

171-176

issue

2

eissn

0006-4971

issn

1528-0020

pii

blood-2016-06-723742

journal_volume

129

pub_type

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