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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)213-236
Number of pages24
JournalCMGH
Volume15
Issue number1
DOIs
StatePublished - Jan 2023

Bibliographical note

Funding Information:
Funding This research was supported by the Basic Science Research Program through the National Research Foundation of Korea , funded by the Ministry of Education (2017R1A6A3A04009690, 2018R1A5A2025286, 2022R1A2C3007850, 2022M3A9F3016364), and the Korea Mouse Phenotyping Project (NRF-2016M3A9D5A01952416).

Publisher Copyright:
© 2022 The Authors

Keywords

  • Histidine Decarboxylase
  • Hypertrophic Gastropathy
  • Macrophage
  • Stomach

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