c-Rel Is Required for IL-33-Dependent Activation of ILC2s

Aidil Zaini, Thomas S Fulford, Raelene J Grumont, Jessica Runting, Grace Rodrigues, Judy Ng, Steve Gerondakis, Colby Zaph, Sebastian Scheer

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)


Group 2 innate lymphoid cells (ILC2s) are emerging as important cellular regulators of homeostatic and disease-associated immune processes. The cytokine interleukin-33 (IL-33) promotes ILC2-dependent inflammation and immunity, with IL-33 having been shown to activate NF-κB in a wide variety of cell types. However, it is currently unclear which NF-κB members play an important role in IL-33-dependent ILC2 biology. Here, we identify the NF-κB family member c-Rel as a critical component of the IL-33-dependent activation of ILC2s. Although c-Rel is dispensable for ILC2 development, it is critical for ILC2 function in the lung, with c-Rel-deficient ( c-Rel -/- ) mice present a significantly reduced response to papain- and IL-33-induced lung inflammation. We also show that the absence of c-Rel reduces the IL-33-dependent expansion of ILC2 precursors and lower levels of IL-5 and IL-13 cytokine production by mature ILC2s in the lung. Together, these results identify the IL-33-c-Rel axis as a central control point of ILC2 activation and function.

Original languageEnglish
Article number667922
JournalFrontiers in Immunology
Publication statusPublished - 14 Jun 2021
Externally publishedYes


  • Animals
  • Bone Marrow/drug effects
  • Cell Proliferation/drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Immunity, Innate/drug effects
  • Interleukin-13/metabolism
  • Interleukin-33/pharmacology
  • Interleukin-5/metabolism
  • Lung/drug effects
  • Lymphocyte Activation/drug effects
  • Lymphocytes/drug effects
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B p50 Subunit/genetics
  • Papain
  • Pneumonia/chemically induced
  • Proto-Oncogene Proteins c-rel/genetics


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