GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE339nnn/GSE339493/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE339493GEOGSEfalseInterleukin-33 activated group 2 innate lymphoid cells drive type 2 immune dysfunction in endometriosisImmune dysfunction is a key contributor to endometriosis (EM) pathophysiology, with a type 2-skewed immune response thought to support EM lesion maintenance and establishment. The alarmin interleukin-33 (IL-33) is elevated in EM patient plasma, peritoneal fluid (PF), and lesions compared to controls, and in an EM mouse model IL-33 drives lesion progression, although exact mechanisms remain unclear. Here we validate that IL-33/ST2 signaling contributes to EM pathophysiology, identifying IL-33/ST2 axis dysregulation in EM lesions compared to control endometrial tissue and characterize PF group 2 innate lymphoid cells (ILC2s) with upregulation of ST2+ in severe stage patients. Using ILC2-deficient mice, we demonstrate that ILC2s are critical for the IL-33-driven inflammatory response in EM. IL-33 treatment in EM-induced ILC2-deficient mice resulted in reduced type 2 effector cytokine production and dysregulated immune infiltration, as well as an altered lesion transcriptional signature compared to ILC2-sufficient controls. Notably, reintroducing ILC2s was insufficient to rescue the IL-33-mediated response; however, we identified ILC2 homing to EM lesions. Finally, we identify ST2 neutralization as a promising therapeutic technique to blunt the IL-33/ILC2 type 2 response in EM.2026/08/03GSE339493GSM9896533GSM9896511GSM9896512GSM9896534GSM9896535GSM9896513GSM9896536GSM9896514GSM9896515GSM9896537GSM9896538GSM9896516GSM9896539GSM9896517GSM9896518GSM9896530GSM9896531GSM9896532GSM9896510GSM9896508GSM9896509GSM9896544GSM9896522GSM9896523GSM9896545GSM9896546GSM9896524GSM9896547GSM9896525GSM9896526GSM9896548GSM9896527GSM9896528GSM9896529GSM9896540GSM9896541GSM9896520GSM9896542GSM9896543GSM9896521GSM989651924247339493Mus musculus