miR-23b-3p deficiency exacerbates immune dysregulation in immunoglobulin A vasculitis by enhancing TLR4-mediated dendritic cell activation

Abstract

Objective: MicroRNAs (miRNAs) play critical roles in regulating immune cell differentiation and maintaining innate and adaptive immune homeostasis. The aim of this study was to determine the mechanisms by which miR-23b-3p modulates crosstalk between innate and adaptive immunity in immunoglobulin A (IgA) vasculitis (IgAV) and to evaluate its therapeutic potential.

Methods: An IgAV rat model and in vitro cell culture systems were established to assess the effects of miR-23b-3p on dendritic cell (DC) maturation and function via Toll-like receptor 4 (TLR4) signalling and to determine the subsequent impact on T follicular helper (Tfh) cell differentiation mediated by cytokine secretion.

Results: IgAV rats exhibited significantly increased TLR4 expression in peripheral blood mononuclear cells and spleen tissue, accompanied by reduced miR-23b-3p expression. Mechanistic analyses demonstrated that miR-23b-3p directly targeted TLR4 to suppress its expression. In vivo overexpression of miR-23b-3p ameliorated IgAV manifestations, as evidenced by reduced TLR4 expression on DCs, diminished Tfh cell differentiation, and decreased serum levels of IgA, interleukin (IL)-6, and IL-12. Notably, TLR4 silencing reversed miR-23b-3p inhibitor-induced DC hyperactivation and aberrant Tfh cell differentiation.

Conclusion: miR-23b-3p regulates DC maturation and function and subsequent Tfh differentiation in a TLR4-dependent manner. miR-23b-3p deficiency aggravates IgAV by promoting pathogenic DC-Tfh axis activation, whereas restoration of miR-23b-3p expression attenuates immune dysregulation, suggesting a potential therapeutic strategy for IgAV.

Keywords: T follicular helper cells; immunoglobulin A vasculitis; miR-23b-3p; toll-like receptor 4.