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 Activi

To further investigate the role of <i>PKCλ/ι</i> in <i>Schistosoma japonicum</i>-induced hepatic fibrosis, we employed a CD4⁺ T-cell-specific <i>PKCλ/ι</i> 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 <i>PKCλ/ι</i> in the hepatic fibrosis caused by <i>S. japonicum</i> infection. Flow cytometry, RT-qPCR and ELISA were used to analyze the effects of <i>PKCλ/ι</i> 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 <i>PKCλ/ι</i> deficiency led to altered BCR signaling gene expression, reduced germinal center activity, and decreased anti-SEA antibody levels. Tfh cells and key factors including <i>IL-21</i>, <i>CXCR5</i>, and <i>ICOS</i> 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 <i>PKCλ/ι</i> 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.