Hematopoietic stem and progenitor cells integrate microbial signals to promote post-inflammation gut tissue repair

EMBO J. 2022 Nov 17;41(22):e110712. doi: 10.15252/embj.2022110712. Epub 2022 Oct 18.

Abstract

Bone marrow (BM)-resident hematopoietic stem and progenitor cells (HSPCs) are often activated following bacterial insults to replenish the host hemato-immune system, but how they integrate the associated tissue damage signals to initiate distal tissue repair is largely unknown. Here, we show that acute gut inflammation expands HSPCs in the BM and directs them to inflamed mesenteric lymph nodes through GM-CSFR activation for further expansion and potential differentiation into Ly6C+ /G+ myeloid cells specialized in gut tissue repair. We identified this process to be mediated by Bacteroides, a commensal gram-negative bacteria that activates innate immune signaling. These findings establish cross-organ communication between the BM and distant inflamed sites, whereby a certain subset of multipotent progenitors is specified to respond to imminent hematopoietic demands and to alleviate inflammatory symptoms.

Keywords: Bacteroides; hematopoietic stem and progenitor cells; innate immune signaling; tissue-repairing cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Hematopoietic Stem Cells* / physiology
  • Humans
  • Inflammation* / pathology
  • Myeloid Cells / pathology
  • Signal Transduction

Associated data

  • GEO/GSE207403