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

Na Fu; Feijing Wu; Zhengyu Jiang; Woosook Kim; Tuo Ruan; Ermanno Malagola; Yosuke Ochiai; Osmel Companioni Nápoles; Giovanni Valenti; Ruth A. White; Bryana R. Belin; Leah B. Zamechek; Jonathan S. LaBella; Timothy C. Wang

Cellular and Molecular Gastroenterology and Hepatology (Jan 2021)

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

Na Fu,
Feijing Wu,
Zhengyu Jiang,
Woosook Kim,
Tuo Ruan,
Ermanno Malagola,
Yosuke Ochiai,
Osmel Companioni Nápoles,
Giovanni Valenti,
Ruth A. White,
Bryana R. Belin,
Leah B. Zamechek,
Jonathan S. LaBella,
Timothy C. Wang

Affiliations

Na Fu: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York; Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
Feijing Wu: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York; The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
Zhengyu Jiang: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Woosook Kim: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Tuo Ruan: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
Ermanno Malagola: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Yosuke Ochiai: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Osmel Companioni Nápoles: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Giovanni Valenti: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Ruth A. White: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Bryana R. Belin: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Leah B. Zamechek: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Jonathan S. LaBella: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Timothy C. Wang: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York; Correspondence Address correspondence to: Timothy C. Wang, MD, Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, Irving Cancer Research Center, 1130 St. Nicholas Avenue, New York, New York, 10032. fax: (212) 851-4590.

Journal volume & issue: Vol. 11, no. 4
pp. 1119 – 1138

Abstract

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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.

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

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