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DAB2IP modulates intestinal inflammation by enhancing ILC3 function in the gut
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DOI：10.1093/jimmun/vkag050.png)
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Abstract
En 中文
Group 3 innate lymphoid cells (ILC3s) preserve intestinal barrier integrity by producing IL-22 and IL-17A, yet the molecular mechanisms that maintain these cytokines during inflammation are incompletely defined. Here, we identify DAB2IP as a cell-intrinsic regulator of ILC3 effector function. In human inflammatory bowel disease mucosa, DAB2IP expression is reduced and associated with transcriptional programs linked to impaired epithelial repair. In murine models, inflammatory cues dynamically modulate Dab2ip in ILC3s, and genetic loss of DAB2IP diminishes IL-22 and IL-17A, compromising host defense during Citrobacter rodentium infection, and exacerbates dextran sulfate sodium-induced colitis. Mechanistically, DAB2IP enables efficient NF-kappa B activation, promoting I kappa B alpha degradation, p65 nuclear accumulation, and thus transcription of Il22/Il17a and NF-kappa B targets. These results reveal a context-dependent role for DAB2IP as a positive regulator of NF-kappa B in ILC3s, highlighting its previously unknown function in mucosal immunity and epithelial repair, and suggesting that restoring DAB2IP signaling could enhance barrier protection during intestinal inflammation.
Keywords:
cytokine production
DAB2IP
innate immunity
innate lymphoid cells 3 (ILC3)
mucosal immunity
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3.7W
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9.9W
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