B lymphocytopenia and Bregs in a not-to-die murine sepsis model

Kensuke Umakoshi; Mohammed E Choudhury; Ryutaro Nishioka; Hironori Matsumoto; Naoki Abe; Yuki Nishikawa; Satoshi Kikuchi; Jun Takeba; Hajime Yano; Toshihiro Yorozuya; Norio Sato; Mayuki Aibiki; Junya Tanaka

doi:10.1016/j.bbrc.2019.12.041

B lymphocytopenia and Bregs in a not-to-die murine sepsis model

Biochem Biophys Res Commun. 2020 Feb 26;523(1):202-207. doi: 10.1016/j.bbrc.2019.12.041. Epub 2019 Dec 14.

Authors

Affiliations

¹ Department of Emergency and Critical Medicine, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan; Advanced Emergency and Critical Care Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan.
² Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
³ Department of Emergency and Critical Medicine, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
⁴ Department of Anesthesia and Perioperative Medicine, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
⁵ Department of Aeromedical Services for Emergency and Trauma Care, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
⁶ Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan. Electronic address: jtanaka@m.ehime-u.ac.jp.

PMID: 31843193
DOI: 10.1016/j.bbrc.2019.12.041

Abstract

Sepsis is a leading cause of mortality in intensive care units due to multi-organ failure caused by dysregulated immune reactions. In this study, kinetic changes in the immune system were analyzed for 72 h in cecal ligation and puncture (CLP)-induced septic mice while preventing animal death by keeping body temperature. Increase of myeloid cells and decrease of B cells in circulation at 6 h after CLP were markedly observed. At the same time point, interleukin (IL)-10 expressing CD5⁺ regulatory B cells (Bregs) appeared. IL-10 and programmed death-ligand 1 (PD-L1) mRNA as well as IL-1β, IL-6 and interferon γ (IFNγ) mRNA was increased in the spleen at 6 h. A gradual decrease in Bcl-2 and abrupt increase of Bim expression in the spleen at the late phase were also found. These results showed that B lymphocytopenia with the appearance of Bregs is the earliest event, likely leading to immunoparalysis in sepsis.

Keywords: Apoptosis; Flow cytometry; Hypothermia; IL-10; PD-L1.

Publication types

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

MeSH terms

Animals
B-Lymphocytes, Regulatory / immunology*
Cecum / surgery
Disease Models, Animal*
Lymphopenia / immunology*
Male
Mice
Mice, Inbred C57BL
Punctures
Sepsis / immunology*