Noncanonical NF-κB pathway driven inflammation across multiple cellular compartments identifies NIK as a therapeutic target for inflammatory bowel disease - Takeaways - MDSpire
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Targeting NIK in the Noncanonical NF-κB Pathway Reveals Inflammatory Mechanisms in Diverse Cellular Compartments Relevant to Inflammatory Bowel Disease

  • By

  • Hao Xu

  • Dun Li

  • Jie Liang

  • Nathan Adamson

  • Alexis Scherl

  • Luli Zou

  • Crystal Hu

  • Elaine E. Storm

  • Christian B. Cox

  • Adam Johnson

  • Mary E. Keir

  • Hua Zhang

  • Saiyu Hang

  • June 9, 2026

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  • 1

    The noncanonical NF-κB pathway, driven by NIK, is crucial in the pathogenesis of inflammatory bowel disease (IBD).

  • 2

    NIK deletion in epithelial cells impairs M-cell differentiation and reduces recruitment of Th17 cells and ILC3s in IBD models.

  • 3

    NIK activity in dendritic cells enhances CD40-mediated innate immune responses, while in T cells, it promotes pro-inflammatory Th1 differentiation.

  • 4

    Pharmacologic inhibition of NIK with NIK-smi reduced inflammation and improved colon histopathology in preclinical colitis models.

  • 5

    PK/PD modeling indicated that a 200 mg/kg BID dosing regimen of NIK-smi optimally inhibited the pathway and enhanced therapeutic efficacy.

Original Source(s)

Noncanonical NF-κB pathway driven inflammation across multiple cellular compartments identifies NIK as a therapeutic target for inflammatory bowel disease

  • by Hao Xu, Dun Li, Jie Liang, Nathan Adamson, Alexis Scherl, Luli Zou, Crystal Hu, Elaine E. Storm, Christian B. Cox, Adam Johnson, Mary E. Keir, Hua Zhang, Saiyu Hang

  • June 9, 2026

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