ETH Zurich: IκBζ regulates ILC2 effector functions; mice lacking it clear hookworm slower
In mice, the transcriptional regulator IκBζ controls cytokine production and proliferation of ILC2 cells. Without it, hookworm clearance is delayed and airway inflammation is reduced.
A team from ETH Zurich, the University of Zurich, the University of Geneva and other institutions reported that the transcriptional regulator IκBζ is essential for the effector functions of group 2 innate lymphoid cells (ILC2). The work, in mice, was published on 9 November 2026 in Nature Communications nature.com
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ILC2s are sentinel cells that maintain tissue homeostasis and take part in the immune response to helminths by secreting type 2 cytokines. IκBζ is an atypical member of the IκB family. According to the authors, it controls basal IL-5 production by ILC2s and governs their effector program during helminth infection and asthma.
IκBζ expression in ILC2
Peripheral ILC2s express IκBζ at steady state. Its expression increases further after stimulation with IL-33 or IL-25, in an NF-κB- and STAT3/5-dependent manner.
The authors report that after activation IκBζ refines chromatin accessibility at regulatory elements of effector cytokine loci, thereby licensing their transcription nature.com
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Effects of IκBζ deficiency in mice
ILC2s lacking IκBζ secreted less type 2 cytokines and had impaired proliferative capacity. Mice with IκBζ-deficient ILC2s cleared the hookworm Nippostrongylus brasiliensis more slowly than controls.
These mice also showed reduced airway inflammation induced by papain, a model of asthma.
Based on these results, the authors conclude that IκBζ plays a central role in orchestrating the ILC2 effector program in different tissues, in health and in disease nature.com
Nature Communicationsnature.comOpen source ↗. The material does not report experiments in humans or any therapeutic application.
