Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the StomachSummary

Background & Aims: Histamine in the stomach traditionally is considered to regulate acid secretion but also has been reported to participate in macrophage differentiation, which plays an important role in tissue homeostasis. Therefore, this study aimed to uncover the precise role of histamin...

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Main Authors: Kwang H. Kim, Jihwan Park, Yejin Cho, Soo Young Cho, Buhyun Lee, Haengdueng Jeong, Yura Lee, Ja-Woon Yi, Yeseul Oh, Jin-Jae Lee, Timothy C. Wang, Kyung-Min Lim, Ki Taek Nam
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Cellular and Molecular Gastroenterology and Hepatology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352345X22002004
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author Kwang H. Kim
Jihwan Park
Yejin Cho
Soo Young Cho
Buhyun Lee
Haengdueng Jeong
Yura Lee
Ja-Woon Yi
Yeseul Oh
Jin-Jae Lee
Timothy C. Wang
Kyung-Min Lim
Ki Taek Nam
author_facet Kwang H. Kim
Jihwan Park
Yejin Cho
Soo Young Cho
Buhyun Lee
Haengdueng Jeong
Yura Lee
Ja-Woon Yi
Yeseul Oh
Jin-Jae Lee
Timothy C. Wang
Kyung-Min Lim
Ki Taek Nam
author_sort Kwang H. Kim
collection DOAJ
description Background & Aims: Histamine in the stomach traditionally is considered to regulate acid secretion but also has been reported to participate in macrophage differentiation, which plays an important role in tissue homeostasis. Therefore, this study aimed to uncover the precise role of histamine in mediating macrophage differentiation and in maintaining stomach homeostasis. Methods: Here, we expand on this role using histidine decarboxylase knockout (Hdc-/-) mice with hypertrophic gastropathy. In-depth in vivo studies were performed in Hdc-/- mice, germ-free Hdc-/- mice, and bone-marrow–transplanted Hdc-/- mice. The stomach macrophage populations and function were characterized by flow cytometry. To identify stomach macrophages and find the new macrophage population, we performed single-cell RNA sequencing analysis on Hdc+/+ and Hdc-/- stomach tissues. Results: Single-cell RNA sequencing and flow cytometry of the stomach cells of Hdc-/- mice showed alterations in the ratios of 3 distinct tissue macrophage populations (F4/80+Il1bhigh, F4/80+CD93+, and F4/80-MHC class IIhighCD74high). Tissue macrophages of the stomachs of Hdc-/- mice showed impaired phagocytic activity, increasing the bacterial burden of the stomach and attenuating hypertrophic gastropathy in germ-free Hdc-/- mice. The transplantation of bone marrow cells of Hdc+/+ mice to Hdc-/- mice recovered the normal differentiation of stomach macrophages and relieved the hypertrophic gastropathy of Hdc-/- mice. Conclusions: This study showed the importance of histamine signaling in tissue macrophage differentiation and maintenance of gastric homeostasis through the suppression of bacterial overgrowth in the stomach.
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spelling doaj.art-35fab70803294050bbb6b24755b959c82022-12-22T02:50:05ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2023-01-01151213236Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the StomachSummaryKwang H. Kim0Jihwan Park1Yejin Cho2Soo Young Cho3Buhyun Lee4Haengdueng Jeong5Yura Lee6Ja-Woon Yi7Yeseul Oh8Jin-Jae Lee9Timothy C. Wang10Kyung-Min Lim11Ki Taek Nam12Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of KoreaSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Molecular and Life Science, Hanyang University, Ansan, Republic of KoreaSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of KoreaSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of KoreaSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of KoreaSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Life Science, Hallym University, Chuncheon, Republic of KoreaDivision of Digestive and Liver Diseases, Department of Medicine and Irving Cancer Center, Columbia University, New York, New YorkCollege of Pharmacy, Ewha Womans University, Seoul, Republic of Korea; Correspondence Kyung-Min Lim, PhD, College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea.Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; Ki Taek Nam, DVM, PhD, Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.Background & Aims: Histamine in the stomach traditionally is considered to regulate acid secretion but also has been reported to participate in macrophage differentiation, which plays an important role in tissue homeostasis. Therefore, this study aimed to uncover the precise role of histamine in mediating macrophage differentiation and in maintaining stomach homeostasis. Methods: Here, we expand on this role using histidine decarboxylase knockout (Hdc-/-) mice with hypertrophic gastropathy. In-depth in vivo studies were performed in Hdc-/- mice, germ-free Hdc-/- mice, and bone-marrow–transplanted Hdc-/- mice. The stomach macrophage populations and function were characterized by flow cytometry. To identify stomach macrophages and find the new macrophage population, we performed single-cell RNA sequencing analysis on Hdc+/+ and Hdc-/- stomach tissues. Results: Single-cell RNA sequencing and flow cytometry of the stomach cells of Hdc-/- mice showed alterations in the ratios of 3 distinct tissue macrophage populations (F4/80+Il1bhigh, F4/80+CD93+, and F4/80-MHC class IIhighCD74high). Tissue macrophages of the stomachs of Hdc-/- mice showed impaired phagocytic activity, increasing the bacterial burden of the stomach and attenuating hypertrophic gastropathy in germ-free Hdc-/- mice. The transplantation of bone marrow cells of Hdc+/+ mice to Hdc-/- mice recovered the normal differentiation of stomach macrophages and relieved the hypertrophic gastropathy of Hdc-/- mice. Conclusions: This study showed the importance of histamine signaling in tissue macrophage differentiation and maintenance of gastric homeostasis through the suppression of bacterial overgrowth in the stomach.http://www.sciencedirect.com/science/article/pii/S2352345X22002004Histidine DecarboxylaseMacrophageHypertrophic GastropathyStomach
spellingShingle Kwang H. Kim
Jihwan Park
Yejin Cho
Soo Young Cho
Buhyun Lee
Haengdueng Jeong
Yura Lee
Ja-Woon Yi
Yeseul Oh
Jin-Jae Lee
Timothy C. Wang
Kyung-Min Lim
Ki Taek Nam
Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the StomachSummary
Cellular and Molecular Gastroenterology and Hepatology
Histidine Decarboxylase
Macrophage
Hypertrophic Gastropathy
Stomach
title Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the StomachSummary
title_full Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the StomachSummary
title_fullStr Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the StomachSummary
title_full_unstemmed Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the StomachSummary
title_short Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the StomachSummary
title_sort histamine signaling is essential for tissue macrophage differentiation and suppression of bacterial overgrowth in the stomachsummary
topic Histidine Decarboxylase
Macrophage
Hypertrophic Gastropathy
Stomach
url http://www.sciencedirect.com/science/article/pii/S2352345X22002004
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