Thomas, S. Y. | Search bioRxiv

bioRxiv2025

Analysis of menstrual effluent uncovers endometriosis-specific cell populations and impaired cellular pathway processes

Endometriosis is a chronic gynecological disease affecting 1 in 10 reproductive-aged women and is characterized by the ectopic presence of endometrial tissue outside the uterus. The leading hypothesis for disease etiology is via the reflux of menstrual effluent (ME) into the peritoneal cavity. ME is a complex mixture of viable endometrial tissue, proteins, and immune cells which serve specialized functions during menstruation to support and repair the endometrium. We hypothesized shifts in the subpopulations of immune cells present during retrograde menstruation may alter the microenvironment of the peritoneal cavity leading to a favorable environment for uterine tissue attachment and survival of endometriotic lesions. Menstrual effluent collected on days 1 and 2 of menstruation identified from women with endometriosis distinct morphological features, increased subpopulations of aged neutrophils, increased anti-inflammatory macrophages, and overall impaired clearance pathways that hijack endometrial clearance likely contributing to the development and progression of endometriosis.

immunology↗

bioRxiv2024

Toll-Like-Receptor 5 protects against pulmonary fibrosis by reducing lung dysbiosis

Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation. IPF results from maladaptive responses to lung epithelial injury, but the underlying mechanisms remain unclear. Here, we show that deficiency in the innate immune receptor, toll-like receptor 5 (TLR5), is associated with IPF in humans and with increased susceptibility to epithelial injury and experimental fibrosis in mice, while activation of lung epithelial TLR5 through a synthetic flagellin analogue protects from experimental fibrosis. Mechanistically, epithelial TLR5 activation induces antimicrobial gene expression and ameliorates dysbiosis after lung injury. In contrast, TLR5 deficiency in mice and IPF patients is associated with lung dysbiosis. Elimination of the microbiome in mice through antibiotics abolishes the protective effect of TLR5 and reconstitution of the microbiome rescues the observed phenotype. In aggregate, TLR5 deficiency is associated with IPF and dysbiosis in humans and in the murine model of pulmonary fibrosis. Furthermore, TLR5 protects against pulmonary fibrosis in mice and this protection is mediated by effects on the microbiome. One-sentence summaryDeficiency in the innate immune receptor TLR5 is a risk factor for pulmonary fibrosis, because TLR5 prevents microbial dysbiosis after lung injury.

immunology↗