A Subset of Breg Cells, B10, Contributes to the Development of Radiation-Induced Pulmonary Fibrosis

Xiaoxian Pan; Caihong Wang; Yuping Zhan; Jinmei Chen; Zeng Wang; Ruilong Lan; Junying Chen; Weijian Zhang; Chun Chen; Mingwei Zhang; Fei Huang; Jinsheng Hong

doi:10.1016/j.ijrobp.2023.03.077

A Subset of Breg Cells, B10, Contributes to the Development of Radiation-Induced Pulmonary Fibrosis

Int J Radiat Oncol Biol Phys. 2023 Sep 1;117(1):237-251. doi: 10.1016/j.ijrobp.2023.03.077. Epub 2023 Apr 11.

Authors

Xiaoxian Pan¹, Caihong Wang¹, Yuping Zhan¹, Jinmei Chen², Zeng Wang³, Ruilong Lan⁴, Junying Chen³, Weijian Zhang², Chun Chen⁵, Mingwei Zhang², Fei Huang⁶, Jinsheng Hong⁷

Affiliations

¹ Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical Universisty, Fuzhou 350212, China.
² Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical Universisty, Fuzhou 350212, China; Key Laboratory of Radiation Biology of Fujian higher education institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
³ Key Laboratory of Radiation Biology of Fujian higher education institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Central Lab, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
⁴ Provincial Key Laboratory of Precision Medicine for Cancer, Fuzhou 350005, China; Central Lab, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
⁵ School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
⁶ Provincial Key Laboratory of Precision Medicine for Cancer, Fuzhou 350005, China; Central Lab, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China. Electronic address: feifeigood2148@126.com.
⁷ Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical Universisty, Fuzhou 350212, China; Key Laboratory of Radiation Biology of Fujian higher education institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China. Electronic address: hjs703@126.com.

PMID: 37054996
DOI: 10.1016/j.ijrobp.2023.03.077

Abstract

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a serious side effect of radiation therapy, but the underlying mechanisms are unknown. B10 cells, as negative B regulatory cells, play important roles in regulating inflammation and autoimmunity. However, the role of B10 cells in RIPF progression is unclear. The aim of this study was to determine the role of B10 cells in aggravating RIPF and the underlying mechanism.

Methods and materials: The role of B10 cells in RIPF was studied by constructing mouse models of RIPF and depleting B10 cells with an anti-CD22 antibody. The mechanism of B10 cells in RIPF was further explored through cocultivation of B10 cells and MLE-12 or NIH3T3 cells and administration of an interleukin (IL)-10 antibody to block IL-10.

Results: B10 cell numbers increased significantly during the early stage in the RIPF mouse models compared with the controls. In addition, depleting B10 cells with the anti-CD22 antibody attenuated the development of lung fibrosis in mice. Subsequently, we confirmed that B10 cells induced epithelial-mesenchymal transition and the transformation of myofibroblasts via activation of STAT3 signaling in vitro. After blockade of IL-10, it was verified that IL-10 secreted by B10 cells mediates the epithelial-mesenchymal transition of myofibroblasts, thereby promoting RIPF.

Conclusions: Our study uncovers a novel role for IL-10-secreting B10 cells that could be a new target of research for relieving RIPF.

Publication types

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

MeSH terms

Animals
B-Lymphocytes, Regulatory*
Disease Models, Animal
Epithelial-Mesenchymal Transition
Interleukin-10
Mice
NIH 3T3 Cells
Pulmonary Fibrosis* / etiology

Substances

Interleukin-10