Touxie Quyin Compound regulates histone lactylation-mediated Fabp4/5 and tissue-resident memory T cells to improve psoriasis recurrence in mice

Formula PSORI-CM01 has been used to alleviate psoriasis symptoms. Here, we developed a novel formula, Touxie Quyin Compound (TQC), which is composed of PSORI-CM01 and Artemisia annua. This study evaluated its therapeutic effects and the underlying mechanisms mediated by histone lactylation in psoriasis recurrence. Imiquimod (IMQ) was applied to induce psoriasis-like lesions in mice, with vaseline, PSORI-CM01, and TQC treatments used for comparison. After a 7-day IMQ treatment and 30-day drug-free interval, mice were re-challenged to induce psoriasis relapse and subsequently treated with PSORI-CM01 and TQC. PSORI-CM01 and TQC markedly alleviated psoriatic symptoms and reduced H3K18 lactylation in the IMQ group, with TQC showing greater inhibiting effect. ChIP-seq data revealed that genes with hypomodified H3K18la peaks in the IMQ + TQC group compared to the IMQ group were related to lipid metabolism, and transcriptomic analysis also indicated TQC-downregulated genes were associated with lipid metabolism. Correspondingly, TQC reduced the H3K18 lactylation and expression of lipid uptake-related genes Fabp4/5 in psoriatic skin lesions of mice. In addition, the infiltration levels of CD8⁺CD103⁺ tissue-resident memory T (TRM) cells in IMQ mice, as well as the expression of Fabp4/5 within CD3⁺ T cells, could also be reduced by TQC. Lactate treatment reversed the inhibitory effect of TQC on CD8⁺CD103⁺ TRM cells. Collectively, TQC may alleviate psoriasis recurrence by suppressing histone lactylation-mediated Fabp4/5 and CD8⁺CD103⁺ TRM cell infiltration, highlighting its potential as a therapeutic strategy for preventing disease relapse.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04682-y.