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

Ravelojaona, M., Girouard, J., Vaillancourt, C., Van Themsche, C. et Reyes-Moreno, C. (2026). LIF and Oncostatin M mitigate LPS-induced acute endometritis via distinct immunoregulatory mechanisms in peritoneal macrophages in vivo. iScience, 29 (6). ISSN 2589-0042 DOI 10.1016/j.isci.2026.116046

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Résumé

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.

Type de document:	Article
Mots-clés libres:	Cancer Immunology Microenvironment
Date de dépôt:	10 juin 2026 15:03
Dernière modification:	10 juin 2026 15:03
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/12935

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