Hematopoietic stem and progenitor cells integrate microbial signals to promote post‐inflammation gut tissue repair. (18th October 2022)

• Record Type: Journal Article
• Authors: Sezaki, Maiko; Hayashi, Yoshikazu; Nakato, Gaku; Wang, Yuxin; Nakata, Sayuri; Biswas, Subinoy; Morishima, Tatsuya; Fakruddin, Md; Moon, Jieun; Ahn, Soyeon; Kim, Pilhan; Miyamoto, Yuji; Baba, Hideo; Fukuda, Shinji; Takizawa, Hitoshi
• Is Part Of: EMBO journal. Volume 41:Number 22(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-18
• Subjects: Bacteroides -- hematopoietic stem and progenitor cells -- innate immune signaling -- tissue‐repairing cells; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2022110712
• Languages: English
• ISSNs: 0261-4189

Abstract

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. Synopsis: How the hematopoietic system responds to and manages infiltrating microbial signals under pathophysiological conditions has remained unclear. Here, a DSS‐induced acute colitis model was used to reveal how hematopoietic stem cells and progenitor cells (HSPCs) relay microbiota signals to promote tissue repair. Acute gut inflammation causes expansion and myeloid‐directed differentiation of bone marrow (BM) HSPCs, some of which migrate to inflamed mesenteric lymph nodes. Gut‐resident Bacteroides directs BM multipotent progenitor expansion and migration towards mesenteric lymph nodes via GM–CSF and innate immune signaling. Ly6C + /G + cells with an immunosuppressive phenotype accumulate both in the mesenteric lymph node and gut to promote tissue repair. Depletion of Ly6C + /G + cells with a neutralizing antibody exacerbates DSS‐induced colitis while the adoptive transfer of Ly6C + /G + containing MLN cells alleviates gut tissue damage. Abstract : Acute inflammation in the mouse gut causes Bacteroides to direct the expansion and migration of BM HSPCs to mesenteric lymph nodes through activation of GM–CSF.