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Intestinal non-canonical NFκB signaling shapes the local and systemic immune response

Author

Listed:
  • Sadeesh K. Ramakrishnan

    (University of Pittsburgh)

  • Huabing Zhang

    (University of Michigan)

  • Xiaoya Ma

    (University of Michigan)

  • Inkyung Jung

    (University of Michigan)

  • Andrew J. Schwartz

    (University of Michigan)

  • Daniel Triner

    (University of Michigan)

  • Samantha N. Devenport

    (University of Michigan)

  • Nupur K. Das

    (University of Michigan)

  • Xiang Xue

    (University of Michigan)

  • Melody Y. Zeng

    (University of Michigan
    University of Michigan)

  • Yinling Hu

    (National Institutes of Health)

  • Richard M. Mortensen

    (University of Michigan)

  • Joel K Greenson

    (University of Michigan)

  • Marilia Cascalho

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Christiane E. Wobus

    (University of Michigan)

  • Justin A. Colacino

    (University of Michigan
    University of Michigan)

  • Gabriel Nunez

    (University of Michigan
    University of Michigan)

  • Liangyou Rui

    (University of Michigan
    University of Michigan)

  • Yatrik M. Shah

    (University of Michigan
    University of Michigan)

Abstract

Microfold cells (M-cells) are specialized cells of the intestine that sample luminal microbiota and dietary antigens to educate the immune cells of the intestinal lymphoid follicles. The function of M-cells in systemic inflammatory responses are still unclear. Here we show that epithelial non-canonical NFkB signaling mediated by NFkB-inducing kinase (NIK) is highly active in intestinal lymphoid follicles, and is required for M-cell maintenance. Intestinal NIK signaling modulates M-cell differentiation and elicits both local and systemic IL-17A and IgA production. Importantly, intestinal NIK signaling is active in mouse models of colitis and patients with inflammatory bowel diseases; meanwhile, constitutive NIK signaling increases the susceptibility to inflammatory injury by inducing ectopic M-cell differentiation and a chronic increase of IL-17A. Our work thus defines an important function of non-canonical NFkB and M-cells in immune homeostasis, inflammation and polymicrobial sepsis.

Suggested Citation

  • Sadeesh K. Ramakrishnan & Huabing Zhang & Xiaoya Ma & Inkyung Jung & Andrew J. Schwartz & Daniel Triner & Samantha N. Devenport & Nupur K. Das & Xiang Xue & Melody Y. Zeng & Yinling Hu & Richard M. Mo, 2019. "Intestinal non-canonical NFκB signaling shapes the local and systemic immune response," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08581-8
    DOI: 10.1038/s41467-019-08581-8
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