Mouse and human Notch-1 regulate mucosal immune responses

D. R. Mathern, L. E. Laitman, Z. Hovhannisyan, D. Dunkin, S. Farsio, T. J. Malik, G. Roda, A. Chitre, A. C. Iuga, G. Yeretssian, M. C. Berin, S. Dahan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


The Notch-1 signaling pathway is responsible for homeostatic tight junction expression in vitro, and promotes barrier function in vivo in the RAG1-adoptive transfer model of colitis. In this study, we sought to determine the role of colonic Notch-1 in the lymphoepithelial crosstalk in health and disease. We utilized in vivo and in vitro knockdown to target the expression of Notch-1. We identified that epithelial Notch-1 is required for appropriate activation of intestinal epithelial cells at steady state and upon inflammatory stimulus. Notch-1 expression modulates mucosal chemokine and cytokine secretion, and FoxP3 and effector T-cell responses. We showed that epithelial Notch-1 controls the immune function of the epithelium through crosstalk with the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathways that, in turn, elicits T-cell responses. Overall, epithelial Notch-1 bridges innate and adaptive immunity in the gut. Our findings highlight an indispensable role for Notch-1-mediated signaling in the intricate epithelial-immune crosstalk, and validate that epithelial Notch-1 is necessary and sufficient to support protective epithelial proinflammatory responses.

Original languageEnglish (US)
Pages (from-to)995-1005
Number of pages11
JournalMucosal Immunology
Issue number4
StatePublished - Jul 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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