SerpinB9 sustains CIITA to orchestrate MHC-II expression and Th1 differentiation in β-glucan-induced macrophages

Whole glucan particles (WGP) enhance macrophage immune function, while serine protease inhibitor B9 (SerpinB9)-a molecule known to promote tumor immune escape-has an unclear role in WGP-induced macrophage function. In this study, we found that SerpinB9 knockout in WGP-induced bone marrow-derived macrophages (BMDMs) significantly downregulated surface MHC-II expression, reduced TNF-α secretion, and impaired their ability to induce Th1 cell differentiation. Transcriptome analysis revealed that CIITA, the core regulator of MHC-II transcription, was markedly downregulated in SerpinB9-knockout BMDMs. Further experiments confirmed that CIITA knockdown decreased BMDM surface MHC-II expression, whereas CIITA overexpression rescued MHC-II expression in SerpinB9-knockout BMDMs and restored their capacity to induce Th1 cell differentiation. In conclusion, this study demonstrates that under WGP induction, SerpinB9 regulates macrophage MHC-II expression and Th1 differentiation-inducing ability by maintaining CIITA expression, providing new insights into macrophage immune regulation mechanisms.