# Depletion of IgG-producing plasma cells in the colon by treatment of proteasome inhibitor ameliorates chronic DSS-induced colitis in mice

## TL;DR

This study shows that reducing IgG-producing plasma cells in the colon with a proteasome inhibitor helps treat chronic colitis in mice.

## Contribution

The study demonstrates that plasma cell depletion using bortezomib ameliorates colitis and intestinal fibrosis in a mouse model.

## Key findings

- Bortezomib reduced IgG and pANCA levels and IgG-producing plasma cells in the colon.
- Depletion of plasma cells ameliorated colitis and intestinal fibrosis in mice.
- IgG-producing plasma cells were found to contribute to colitis pathogenesis.

## Abstract

Basal plasmacytosis is a histopathological hallmark of ulcerative colitis (UC). However, the precise roles of plasma cells in UC pathogenesis remain unknown. In this study, we investigated the effects of a proteasome inhibitor, which depletes plasma cells, on chronic colitis progression in mice to clarify their contribution to disease pathogenesis. Chronic colitis was induced in female C57BL/6 mice by three cycles of ad libitum dextran sulfate sodium (DSS) feeding followed by distilled water (DW), each cycle lasting seven days. The proteasome inhibitor bortezomib was administered intravenously twice weekly for three weeks after the second DSS/DW cycle. Elevated plasma IgG and perinuclear anti-neutrophil cytoplasmic antibody (pANCA) levels, as well as infiltration of IgG-producing plasma cells into the colon, were observed after the second DSS/DW cycle in chronic DSS-induced colitis model mice. Plasma cells in the colon exhibited an immature CD19⁺CD138⁺ phenotype. Bortezomib significantly ameliorated colitis and intestinal fibrosis by reducing plasma IgG and pANCA levels and the number of IgG-producing plasma cells in the colon. In conclusion, IgG-producing plasma cells were involved in colitis pathogenesis, and their depletion ameliorated colitis. Thus, IgG-producing plasma cells are associated with colitis pathogenesis and potential therapeutic targets for UC.

The online version contains supplementary material available at 10.1038/s41598-025-34868-6.