Jieduquyuziyin prescription suppresses the activation of the extrafollicular effector B cell by regulating integrin αV signaling in systemic lupus erythematosus.

ETHNOPHARMACOLOGICAL RELEVANCE: Jieduquyuziyin Prescription (JP) is an evidence-based herbal formula used to treat systemic lupus erythematosus (SLE). Its efficacy in reducing double-stranded DNA antibodies (dsDNA) has been confirmed by clinical trials and experiments. These results highlight the important value of maintenance of B cell immune homeostasis through integration of ethnopharmacology.

AIM OF THE STUDY: Extrafollicular effector B cell subsets are the primary source of dsDNA antibodies in SLE. This study investigated the mechanism of extrafollicular effector B cells in SLE treated by JP.

METHODS

SLE, Sjögren's Syndrome (SS) patients and healthy controls (HCs) were assessed for double negative 2 B cells (DN2 B) using flow cytometry. Network pharmacology and GEO datasets identified stargets of JP and mechanisms on DN2 B cells. MRL/lpr mice were randomly divided into model (MOD), JP and prednisone (Pred) groups for evaluating level and function of extrafollicular effector B cells, with serum antibodies, cytokines, and renal function by enzyme-linked immunosorbent assay(ELISA) and renal pathology staining.. Transcriptome sequencing from sorted CD19+B cells in spleen, flow cytometry and immunofluorescence were performed for detecting the B cell subsets frequency and spatial position. Furthermore, the effects of JP on extrafollicular effector B cell were assessed using transwell, real-time qPCR, Western blot and flow cytometry in resiquimod (R848) induced Raji cells.

RESULTS

DN2 B cells expanded in SLE patients and responded to treatment. Integrin αV (ITGAV) in B cells from SLE patients and mice shows potential as a therapeutic target after JP treatment. JP improved renal pathology and reduced levels of ABCs and ITGAV in the extrafollicular zone, alleviating tissue inflammation and antibody production in SLE by regulating extrafollicular effector B cells expressing ZEB2 and ITGAV.

CONCLUSION

JP alleviates tissue inflammation and antibody production in SLE by regulating extrafollicular effector B cells expressing integrin αV signaling, thus restoring immune homeostasis.