Work

LIF and Oncostatin M mitigate LPS-induced acute endometritis via distinct immunoregulatory mechanisms in peritoneal macrophages in vivo

Year: 2026

Type: article

Abstract: Acute endometritis, often triggered by Gram-negative bacterial endotoxins such as lipopolysaccharide (LPS), disrupts endometrial integrity, induces robust pro-inflammatory macrophage activation, and compromises uterine function, potentially leading to infertility and adverse pregnancy outcomes. Here, we demonstrate that IL-6 family cytokines, Leukemia Inhibitory Factor (LIF) and Oncostatin M (OSM), exert complementary yet distinct immunoregulatory effects that mitigate LPS-induced acute endometritis in vivo . Both cytokines preserved endometrial architecture, limited neutrophil and macrophage infiltration, suppressed cytotoxic iNOS expression, and promoted macrophage-mediated tissue repair, with OSM providing superior systemic and hepatoprotective effects. Mechanistically, these outcomes were linked to STAT3-dependent Mφ reprogramming toward anti-inflammatory M2 phenotypes, with OSM additionally engaging SMAD2 pathways to favor CD163 M2 macrophages marker, whereas LIF preferentially induced anti-inflammatory M2 subsets engaging STAT3 alone. Our findings highlight the therapeutic potential of LIF and OSM as modulators of uterine immune homeostasis and macrophage plasticity modulating and mitigating LPS-acute endometritis and preserving endometrial integrity.

Source: iScience

DOI: 10.1016/j.isci.2026.116046

Authors: Marion Ravelojaona, Julie Girouard, Cathy Vaillancourt, Céline Van Themsche, Carlos Reyes-Moreno

Institutions: Réseau Québécois en reproduction, Université du Québec, Université du Québec à Trois-Rivières, Université de Montréal, Institut National de la Recherche Scientifique

Language: English

Topic: Reproductive System and Pregnancy

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240