Cyproconazole, a triazole fungicide, drives human immune dysfunction by impairing regulatory B cell activity and inducing T cell senescence

Background. Triazole fungicides, including cyproconazole (CPZ), are among the most widely applied agricultural chemicals globally. While their endocrine-disrupting properties are recognized, their impact on human lymphocyte homeostasis, particularly on immunoregulatory and senescence-associated mechanisms, remains poorly characterized.

Objective. This study investigated the cellular and molecular mechanisms by which CPZ induces immunotoxicity in primary human immune cells, with a focus on regulatory B cell (Breg) function and T lymphocyte senescence.

Methods. Primary peripheral blood mononuclear cells (PBMCs) and purified B and T lymphocyte subsets isolated from healthy donors were exposed to CPZ (30–200 µM, 24–72 h). Cell viability, proliferation, and cell cycle distribution were assessed by flow cytometry. Breg immunosuppressive capacity was evaluated in lymphocyte co-culture assays. T cell senescence was characterized by quantification of surface markers (CD57, CD28, CD27, PD-1) and SASP-associated cytokine secretion was assessed by ELISA. Data were analyzed using one-way ANOVA with Tukey's post hoc test.

Results. CPZ concentration- and time-dependently impaired B cell homeostasis and abrogated Breg-mediated immunosuppression, resulting in a shift toward a pro-inflammatory cytokine milieu. Concurrently, CPZ drove T lymphocytes toward a senescent phenotype, characterized by G0/G1 cell cycle arrest, apoptosis resistance, downregulation of co-stimulatory molecules (CD28, CD27), and acquisition of a Senescence-Associated Secretory Phenotype (SASP) with elevated pro-inflammatory cytokine release (p<0.05).

Conclusion: CPZ disrupts human immune regulation through two converging mechanisms: dismantling Breg-mediated immunological tolerance and accelerating T cell-driven chronic inflammation. These findings provide a mechanistic basis for reconsidering the immunotoxicological risk profile of triazole fungicides and support revised regulatory safety thresholds for occupational and environmental exposures.