Single cell transcriptome analyses reveal the roles of B cells in fructose-induced hypertension

Cheong-Wun Kim; Sung Yong Joo; Boa Kim; Jee Young Kim; Sungmin Jang; Shiang-Jong Tzeng; Sang Jin Lee; Myunghoo Kim; Inkyeom Kim

doi:10.3389/fimmu.2023.1279439

Single cell transcriptome analyses reveal the roles of B cells in fructose-induced hypertension

Front Immunol. 2023 Nov 17:14:1279439. doi: 10.3389/fimmu.2023.1279439. eCollection 2023.

Authors

Cheong-Wun Kim¹, Sung Yong Joo², Boa Kim³, Jee Young Kim¹, Sungmin Jang¹, Shiang-Jong Tzeng⁴, Sang Jin Lee⁵, Myunghoo Kim², Inkyeom Kim¹

Affiliations

¹ Department of Pharmacology, BK21 Plus Kyungpook National University (KNU) Biomedical Convergence Program, Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
² Department of Animal Science, Pusan National University, Miryang, Republic of Korea.
³ Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
⁴ Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵ Division of Rheumatology, Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Abstract

Rationale: While the immune system plays a crucial role in the development of hypertension, the specific contributions of distinct immune cell populations remain incompletely understood. The emergence of single-cell RNA-sequencing (scRNA-seq) technology enables us to analyze the transcriptomes of individual immune cells and to assess the significance of each immune cell type in hypertension development.

Objective: We aimed to investigate the hypothesis that B cells play a crucial role in the development of fructose-induced hypertension.

Methods and results: Eight-week-old Dahl salt-sensitive (SS) male rats were divided into two groups and given either tap water (TW) or a 20% fructose solution (HFS) for 4 weeks. Systolic blood pressure was measured using the tail-cuff method. ScRNA-seq analysis was performed on lamina propria cells (LPs) and peripheral blood mononuclear cells (PBMCs) obtained from SS rats subjected to either TW or HFS. The HFS treatment induced hypertension in the SS rats. The analysis revealed 27 clusters in LPs and 28 clusters in PBMCs, allowing for the identification and characterization of various immune cell types within each cluster. Specifically, B cells and follicular helper T (Tfh) cells were prominent in LPs, while B cells and M1 macrophages dominated PBMCs in the HFS group. Moreover, the HFS treatment triggered an increase in the number of B cells in both LPs and PBMCs, accompanied by activation of the interferon pathway.

Conclusions: The significant involvement of B cells in intestinal and PBMC responses indicates their pivotal contribution to the development of hypertension. This finding suggests that targeting B cells could be a potential strategy to mitigate high blood pressure in fructose-induced hypertension. Moreover, the simultaneous increase in follicular B cells and Tfh cells in LPs, along with the upregulation of interferon pathway genes in B cells, underscores a potential autoimmune factor contributing to the pathogenesis of fructose-induced hypertension in the intestine.

Keywords: B cell; hypertension; immunity; interferon pathway; single-cell RNA-sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hypertension* / chemically induced
Hypertension* / genetics
Interferons / metabolism
Leukocytes, Mononuclear*
Lipopolysaccharides / metabolism
Male
Rats
Rats, Inbred Dahl
Single-Cell Gene Expression Analysis

Substances

Lipopolysaccharides
Interferons

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (NRF-2021R1A2B5B02001763, and 2021R1A4A1021617).