Revealing the core immunotoxicity of di-n-pentyl phthalate exposure in murine models using single-cell RNA sequencing

The phthalate derivative di-n-pentyl phthalate (DNPP) is an extensively distributed environmental contaminant that has been implicated in various pathological conditions. The immune system critically regulates disease pathogenesis through complex interactions. However, current toxicological research has failed to comprehensively characterize DNPP-induced immunotoxicity. Therefore, we aimed to systematically assess DNPP-induced alterations within the immune landscape, by conducting single-cell RNA sequencing (scRNA-seq) on murine splenic tissues. We established a DNPP-exposed mouse model by administering various doses of DNPP, alongside complementary in vitro experiments. We found that DNPP exposure markedly decreased peripheral blood leukocyte populations, which notably affected lymphocytes, neutrophils, and monocytes. Moreover, DNPP might attenuate the cytotoxic capacity of CD8⁺ T cells and reduce the proportions of CD4⁺ T_Tem and CD4⁺ T_Treg cells. Furthermore, DNPP may impair immunoglobulin production of B cells, impact the cytotoxicity of NK cells, and alter the antigen-presenting capacity of myeloid cells. Overall, these findings demonstrate that DNPP functions as an environmental immune disruptor and may increase the susceptibility to infectious diseases, malignancies, and immune-related pathologies. Our study provides novel, impactful insights into DNPP-associated health hazards.