JCI Insight (Dec 2021)

IL-33 activates group 2 innate lymphoid cell expansion and modulates endometriosis

  • Jessica E. Miller,
  • Harshavardhan Lingegowda,
  • Lindsey K. Symons,
  • Olga Bougie,
  • Steven L. Young,
  • Bruce A. Lessey,
  • Madhuri Koti,
  • Chandrakant Tayade

Journal volume & issue
Vol. 6, no. 23

Abstract

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Chronic inflammation and localized alterations in immune cell function are suspected to contribute to the progression of endometriosis and its associated symptoms. In particular, the alarmin IL-33 is elevated in the plasma, peritoneal fluid, and endometriotic lesions from patients with endometriosis; however, the exact role of IL-33 in the pathophysiology of endometriosis is not well understood. In this study, we demonstrate, in both humans and a murine model, that IL-33 contributes to the expansion of group 2 innate lymphoid cells (ILC2s), and this IL-33–induced ILC2 expansion modulates the endometriosis lesion microenvironment. Importantly, we show that IL-33 drives hallmarks of severe endometriosis, including elevated inflammation, lesion proliferation, and fibrosis, and that this IL-33–induced aggravation is mediated by ILC2s. Finally, we demonstrate the functionality of IL-33 neutralization as a promising and potentially novel therapeutic avenue for treating the debilitating symptoms of endometriosis.

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