Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the Stomach.
Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the Stomach.
复制标题
DOI：
10.1016/j.jcmgh.2022.09.008
复制
发表时间：
2023
影响因子：
7.2
通讯作者：
Nam, Ki Taek
中科院分区：
文献类型：
--
作者：
Kim, Kwang H.;Park, Jihwan;Cho, Yejin;Cho, Soo Young;Lee, Buhyun;Jeong, Haengdueng;Lee, Yura;Yi, Ja-Woon;Oh, Yeseul;Lee, Jin-Jae;Wang, Timothy C.;Lim, Kyung-Min;Nam, Ki Taek
胃中的组胺传统上被认为是调节胃酸分泌，但也有报道称其参与巨噬细胞分化，在组织稳态中起重要作用。因此，本研究旨在揭示组胺在介导巨噬细胞分化和维持胃内稳态中的确切作用。在这里，我们使用肥厚性胃病的组氨酸脱羧酶敲除（Hdc-/-）小鼠来扩展这一作用。深入的体内研究分别在Hdc-/-小鼠、无菌Hdc-/-小鼠和骨髓移植的Hdc-/-小鼠中进行。流式细胞术检测胃巨噬细胞的数量和功能。为了鉴定胃巨噬细胞并发现新的巨噬细胞群体，我们对胃组织进行了Hdc+/+和Hdc-/-的单细胞RNA测序分析。Hdc-/-小鼠胃细胞的单细胞RNA测序和流式细胞术显示3种不同的组织巨噬细胞群（F4/80+Il1bhigh， F4/80+CD93+和F4/80- mhc类IIhighCD74high）的比例发生变化。Hdc-/-小鼠胃组织巨噬细胞的吞噬活性受损，增加了胃细菌负荷，减轻了无菌Hdc-/-小鼠的肥厚性胃病。将Hdc+/+小鼠骨髓细胞移植给Hdc-/-小鼠，恢复了胃巨噬细胞的正常分化，减轻了Hdc-/-小鼠的肥厚性胃病。本研究表明组胺信号在组织巨噬细胞分化和通过抑制胃内细菌过度生长维持胃内稳态中的重要性。
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. 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. 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. 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.
登录
查看更多内容
影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
8.8
作者：
Hirata K;Suzuki H;Imaeda H;Matsuzaki J;Tsugawa H;Nagano O;Asakura K;Saya H;Hibi T
通讯作者：
Hibi T
影响因子：
6.7
作者：
Czerner, Christoph P.;Klos, Andreas;Neumann, Detlef
通讯作者：
Neumann, Detlef
影响因子：
5.8
作者：
ELLENBOGEN, L;KELLY, RG;STUBBS, CS
通讯作者：
STUBBS, CS
影响因子：
13.3
作者：
Kim, Kwang H.;Choi, Beom K.;Kwon, Byoung S.
通讯作者：
Kwon, Byoung S.