Acute Intestinal Inflammation Depletes/Recruits Histamine-Expressing Myeloid Cells From the Bone Marrow Leading to Exhaustion of MB-HSCsSummary

Cellular and Molecular Gastroenterology and Hepatology

卷:11

Zhengyu Jiang¹  Tuo Ruan²  Leah B. Zamechek²  Ruth A. White²  Osmel Companioni Nápoles²  Feijing Wu²  Ermanno Malagola³  Jonathan S. LaBella⁴  Yosuke Ochiai⁵  Woosook Kim⁵  Na Fu⁵  Timothy C. Wang⁵  Giovanni Valenti⁵  Bryana R. Belin⁵ 

[1] Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;

[2] Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York;

[3] The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China;

[4] Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China;

[5] Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York;

关键词: Histidine Decarboxylase (HDC);    Hematopoietic Stem Cell (HSC);    Myeloid Cell;    Intestine Inflammation;    H2-Receptor (H2R) Agonist;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background & Aims: Histidine decarboxylase (HDC), the histamine-synthesizing enzyme, is expressed in a subset of myeloid cells but also marks quiescent myeloid-biased hematopoietic stem cells (MB-HSCs) that are activated upon myeloid demand injury. However, the role of MB-HSCs in dextran sulfate sodium (DSS)-induced acute colitis has not been addressed. Methods: We investigated HDC+ MB-HSCs and myeloid cells by flow cytometry in acute intestinal inflammation by treating HDC–green fluorescent protein (GFP) male mice with 5% DSS at various time points. HDC+ myeloid cells in the colon also were analyzed by flow cytometry and immunofluorescence staining. Knockout of the HDC gene by using HDC-/-; HDC-GFP and ablation of HDC+ myeloid cells by using HDC-GFP; HDC–tamoxifen-inducible recombinase Cre system; diphtheria toxin receptor (DTR) mice was performed. The role of H2-receptor signaling in acute colitis was addressed by treatment of DSS-treated mice with the H2 agonist dimaprit dihydrochloride. Kaplan–Meier survival analysis was performed to assess the effect on survival. Results: In acute colitis, rapid activation and expansion of MB-HSC from bone marrow was evident early on, followed by a gradual depletion, resulting in profound HSC exhaustion, accompanied by infiltration of the colon by increased HDC+ myeloid cells. Knockout of the HDC gene and ablation of HDC+ myeloid cells enhance the early depletion of HDC+ MB-HSC, and treatment with H2-receptor agonist ameliorates the depletion of MB-HSCs and resulted in significantly increased survival of HDC-GFP mice with acute colitis. Conclusions: Exhaustion of bone marrow MB-HSCs contributes to the progression of DSS-induced acute colitis, and preservation of quiescence of MB-HSCs by the H2-receptor agonist significantly enhances survival, suggesting the potential for therapeutic utility.

【 授权许可】

Unknown