# Conditional Ablation of PKCλ/ι in CD4+ T Cells Ameliorates Hepatic Fibrosis in Schistosoma japonicum-Infected Mice via T Follicular Helper (Tfh) Cell Suppression Coupled with Increased Follicular Regulatory T (Tfr) and Regulatory B (Breg) Cell Activities

## TL;DR

Removing PKCλ/ι in CD4+ T cells in mice reduces liver scarring from a parasitic infection by suppressing harmful immune cells and boosting regulatory cells.

## Contribution

This study reveals a new therapeutic target, PKCλ/ι, for treating liver fibrosis via immune cell regulation.

## Key findings

- PKCλ/ι deficiency reduced T follicular helper (Tfh) cells and key factors like IL-21 and ICOS.
- Deficiency increased follicular regulatory T (Tfr) and regulatory B (Breg) cells, which produce IL-10.
- Liver fibrosis was attenuated due to reduced Tfh activity and enhanced regulatory cell function.

## Abstract

To further investigate the role of PKCλ/ι in Schistosoma japonicum-induced hepatic fibrosis, we employed a CD4+ T-cell-specific PKCλ/ι conditional knockout (KOSJ) mouse model, with wild-type (WTSJ) mice used as controls. Transcriptomic profiling of hepatic mRNA was used to reveal the immune regulatory mechanisms underlying the role of PKCλ/ι in the hepatic fibrosis caused by S. japonicum infection. Flow cytometry, RT–qPCR and ELISA were used to analyze the effects of PKCλ/ι on Tfh and Tfr cells, and single-cell RNA sequencing was used to elucidate the interactions between Tfr and B cells. The results showed that PKCλ/ι deficiency led to altered BCR signaling gene expression, reduced germinal center activity, and decreased anti-SEA antibody levels. Tfh cells and key factors including IL-21, CXCR5, and ICOS were downregulated, while Tfr cells and IL-10+ B cells increased. Additionally, hepatic neutrophils decreased and Treg/Tfr ratios rose, with enhanced IL-10-mediated cellular crosstalk. These findings indicate that PKCλ/ι deficiency attenuates liver fibrosis by inhibiting Tfh differentiation, promoting Tfr function, and activating IL-10-producing Breg cells, suggesting its potential as a therapeutic target.