Pyroptosis orchestrates immune responses in endometriosis

Endometriosis is a refractory and recurrent gynecological condition which affects about 10 % of reproductive-age women. The dysfunctional immune system is a well-established element in disease pathogenesis. Pyroptosis, a novel form of inflammatory cell death, has been revealed to be strongly connected with immune responses in tumors. Nevertheless, its relationship with microenvironment characteristics and clinical features in endometriosis is unclear. Here, we performed bioinformatics analysis on published data in humans and revealed a significant but neglected role of pyroptosis in endometriosis. Samples with higher PyrScores were generally accompanied with more aggressive disease features, such as EMT, angiogenesis and immune disorders. We further confirmed in animal models that pyroptosis exacerbated immune dysfunction by recruiting activated immune cell including macrophages, DC, neutrophils, CD8+ Tcm and Tregs with unregulated CCL2, CCL3, CXCL2 and CXCL3. Collectively, pyroptosis is a distinctive feature of endometriosis. Our work provides insights into further studies targeting pyroptosis for molecular typing and individualized precise therapy.