Excessive Kynurenine Metabolism Impairs Lysosomal acidification and Triggers mtDNA Release via the AHR/CISH/ATP6V1A Axis in Decidual Macrophages Associated with Unexplained Recurrent Pregnancy Loss.

ABSTRACT: Metabolic disturbances of decidual macrophages (dMφs) may contribute to the pathology of miscarriage, yet the underlying mechanisms remain poorly defined. Here, we document upregulated tryptophan metabolic pathway in dMφs from women with unexplained recurrent pregnancy loss (URPL), with increased kynurenine (KYN) levels in the decidua and elevated aryl hydrocarbon receptor (AHR) expression in dMφs. Excessive activation of the KYN-AHR axis compromises both mitochondrial and lysosomal integrity. This impairment facilitates the leakage of mtDNA into the cytoplasm and subsequent release into the extracellular space, thereby activating the cGAS-STING signaling cascade. Mechanistically, AHR directly binds to the xenobiotic response element within the CISH promoter region, promoting its tr

SUBMITTER: Song G 

PROVIDER: S-EPMC12781176 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature