Biology subjects

Bougie, O.

Publications and source records attributed to Bougie, O..

3 recordsLinked to original sources

bioRxiv2026

Endometriosis patient-derived small extracellular vesicles carry unique immune, proteomic and lipidomic signatures associated with mild and severe endometriosis

Endometriosis (EM) is a heterogeneous, gynecological inflammatory disease affecting over 200 million individuals worldwide, yet the mechanisms underlying lesion establishment, progression, and recurrence remain incompletely understood. Small extracellular vesicles (sEVs) mediate intercellular communication through the transfer of proteins, lipids, and nucleic acids reflective of their cellular origin; however, stage- and tissue-specific sEV signatures remain poorly defined. Here, we characterized the molecular and functional landscape of EM-derived sEVs across disease stages and biological sources. sEVs isolated from eutopic endometrium, ectopic lesions, peritoneal fluid, and plasma from mild- and severe-stage EM patients and healthy controls were analyzed by surface marker profiling, proteomics, lipidomics, and integrated multi-omics, with functional effects assessed in human uterine microvascular endothelial cells. sEV composition varied by disease stage and sample type, with EM lesion-derived sEVs demonstrating stage-dependent loss of epithelial-associated markers and enrichment of immune-associated signatures, while EM plasma-derived sEVs exhibited altered adhesion- and platelet-associated profiles. Integrated multi-omics identified coordinated programs associated with immune adaptation, extracellular matrix organization, epithelial remodeling, vascular signaling, oxidative stress, and metabolic adaptation. Functionally, sEVs derived from severe endometriotic lesions exhibited enhanced uptake and mitochondrial localization in endothelial cells and promoted angiogenic activity. Our findings establish sEVs as dynamic mediators of EM disease progression and demonstrate that integrated sEV profiling provides a framework for understanding EM heterogeneity and identifying candidate biomarkers and therapeutic targets.

molecular biology↗

bioRxiv2026

An investigation of the IL-23/Th17 axis and transcriptomic profiles of T helper subsets in endometriosis

Endometriosis (EMS) is a chronic inflammatory disease characterized by ectopic endometrial-like tissue growth and immune dysregulation. Aberrant T cell responses are implicated in EMS pathogenesis, however, functional reprogramming of T helper (Th) subsets across disease stages remain unclear. We profiled systemic and local immune mediators (cytokines/chemokines) and performed bulk RNA sequencing to comprehensively characterize Th1, Th1/17, and Th17 cell subsets from EMS patients and healthy controls. Across patient plasma, peritoneal fluid (PF), and matched eutopic and ectopic tissues, we observed systemic and local cytokine/chemokine alterations, including elevated IL-6 (plasma), FLT-3L and G-CSF (eutopic), and IL-1RA and IL-23 (p40; PF) in severe-stage EMS. Flow cytometry depicted elevated pathogenic Th17 cells in patient PF compared to matched non-pathogenic Th17 and Treg cell subsets. Additionally, circulating Th17 cells were increased in patients with mild (stages I-II) relative to severe (stages III-IV) EMS. RNA sequencing revealed extensive Th subset reprogramming in EMS, most predominately in Th17 cells (2,220 DEGs). Collectively, we reveal significant immune remodeling in EMS and highlight a distinct, aberrant Th17 cell phenotype. Results support repurposing of IL-23- and IL-17-targeted therapeutics, already effectively implemented in other chronic inflammatory diseases, to broaden therapeutic options for EMS and associated comorbidities.

immunology↗

bioRxiv2023

The dysregulated IL-23/TH17 axis in endometriosis pathophysiology

Endometriosis is a chronic inflammatory disease where endometrial-like tissue grows ectopically, resulting in pelvic pain and infertility. Interleukin (IL)-23 is established as a key contributor in the development and differentiation of a subset of T cells known as T-helper 17 (TH17) cells, driving TH17 cells towards a pathogenic profile. In a variety of inflammatory and autoimmune disorders, such as psoriasis and rheumatoid arthritis, TH17 cells secrete proinflammatory cytokines including IL-17, contributing to the disease pathophysiology. Our studies and others have implicated IL-17 and TH17 cell dysregulation in endometriosis, which is associated with disease severity. Here we address whether IL-23 driven TH17 cells contribute to the cardinal features of lesion proliferation, vascularization, and inflammation in endometriosis using patient samples, representative cell lines, and our established mouse model of endometriosis. Our results indicate significantly dysregulated expression of key genes in the IL-23/TH17 axis in patient ectopic and eutopic endometrial samples and increased IL-23 protein in patient plasma compared to healthy controls. In-vitro studies using primary human TH cells determined that IL-23 cocktail treatment significantly increased the frequency of pathogenic TH17 cells. Similarly, treatment with recombinant human (rh)IL-23 on cell lines (12Z, EECC, HUVEC, and hESC) representative of the endometriotic lesion microenvironment led to a significant increase in cytokines and growth factors known to play a role in lesion establishment and maintenance. In a syngeneic mouse model of endometriosis, treatment with recombinant mouse (rm)IL-23 led to significant alterations in numbers of myeloid and T cell subsets in peritoneal fluid and significantly increased numbers of giant cells within the lesion. Endometriotic lesions from rmIL-23 mice did not reveal significant alterations in proliferation and vascularization, although trends of increased proliferation and vascularization were observed. Collectively, these findings provide insights into the impact of the IL-23/TH17 axis on local immune dysfunction and broadly on the pathophysiology of endometriosis.

immunology↗