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Tim-3 Agonist Restrains ILC2 Function and Attenuates Airway Hyperreactivity via NLK Pathway

GSE298909 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2026/02/22 Platform GPL19057
Summary
Allergic asthma is driven by type 2 inflammation involving cytokines such as IL-4, IL-5, and IL-13, with group 2 innate lymphoid cells (ILC2s) playing a key pathogenic role. Here, we identify T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) as a negative regulator of ILC2 function. Tim-3 expression was upregulated in activated pulmonary ILC2s, and engagement with Tim-3 agonists inhibited ILC2 activation, proliferation, and type 2 cytokine production via the NLK signaling pathway and suppression of mitochondrial metabolism. In vivo, Tim-3 agonists alleviated airway hyperreactivity (AHR) and inflammation in both IL-33- and Alternaria alternata-induced AHR models, while ILC2-specific Tim-3 deletion exacerbated AHR. These results were confirmed in human ILC2s and humanized mice, supporting the translational relevance. Our findings establish Tim-3 as an inhibitory checkpoint for ILC2s and suggest its potential as a therapeutic target in allergic asthma and other ILC2-mediated diseases.
Published in
Tim-3 agonist restrains ILC2 function and attenuates airway hyperreactivity via NLK pathway
Sakano Y, Sakano K, Kokubo K et al. · Nature communications 2026 · PMID 41922900 · doi:10.1038/s41467-026-71336-9
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Also filed as BioProject PRJNA1271777 and SRA study SRP589776. Searching any of these in the dataset finder brings you back here.

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