IL-33-ILC2 axis in the female reproductive tract

Trends Mol Med. 2022 Jul;28(7):569-582. doi: 10.1016/j.molmed.2022.04.006. Epub 2022 May 12.


IL-33 is a member of the IL-1 family and was first identified as an alarmin that acts at mucosal barrier sites. However, IL-33 is now understood to be a pleiotropic cytokine that acts on a variety of immune and non-immune cell types to promote type 2 T helper cell (TH2) inflammation as well as to regulate and suppress homeostatic processes. Of particular interest are group 2 innate lymphoid cells (ILC2s) which are activated by IL-33 and promote many IL-33-specific effects. Considerable investigation has surrounded the integral role of IL-33 and ILC2s in driving inflammation in asthma, allergy, atopic dermatitis, fibrotic diseases, microbial interactions, and more. However, IL-33 and ILC2s have also emerged as key components of a healthy pregnancy and fertility; when dysregulated, they can drastically drive female reproductive pathologies. We first summarize the presence of both IL-33 and ILC2s in the female reproductive tract (FRT) and in healthy pregnancy. We then provide insights into how IL-33 and ILC2s drive female reproductive pathologies and how this axis could be a potential therapeutic target in reproductive disorders including preterm birth, pre-eclampsia, recurrent spontaneous abortion, and endometriosis.

Keywords: IL-33; ILC2; infertility; pathology; pregnancy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / metabolism
  • Female
  • Genitalia, Female* / immunology
  • Humans
  • Immunity, Innate*
  • Inflammation
  • Interleukin-33* / metabolism
  • Lymphocytes / metabolism


  • Cytokines
  • Interleukin-33

Grant support