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

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Group 2 innate lymphoid cells (ILC2s) regulate immune responses in homeostasis and disease.
• Interleukin-33 (IL-33) is a key cytokine activating ILC2s and NF-κB signaling.
• The specific NF-κB members involved in IL-33-mediated ILC2 activation remain largely unknown.

Purpose of the Study:

• To identify the role of NF-κB family members in IL-33-dependent ILC2 activation.
• To investigate the function of c-Rel in ILC2 biology and lung inflammation.

Main Methods:

• Utilized c-Rel-deficient mice to assess ILC2 development and function.
• Analyzed lung inflammation responses to papain and IL-33.
• Quantified ILC2 precursor expansion and cytokine production (IL-5, IL-13).

Main Results:

• c-Rel is dispensable for ILC2 development but critical for their function in the lung.
• c-Rel-deficient mice exhibit reduced lung inflammation in response to IL-33 and papain.
• Absence of c-Rel impairs IL-33-induced ILC2 precursor expansion and reduces IL-5 and IL-13 production.

Conclusions:

• The NF-κB member c-Rel is a critical mediator of IL-33-dependent ILC2 activation and function.
• The IL-33-c-Rel axis represents a central regulatory pathway controlling ILC2 responses in the lung.