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Butler M, Chaudhary R, van Heel DA, et al. NOD2 activity modulates the phenotype of LPS-stimulated dendritic cells to promote the development of T-helper type 2-like lymphocytes - Possible implications for NOD2-associated Crohn's disease. J Crohns Colitis. 2007;1(2):106-15doi: 10.1016/j.crohns.2007.08.006.
Butler, M., Chaudhary, R., van Heel, D. A., Playford, R. J., & Ghosh, S. (2007). NOD2 activity modulates the phenotype of LPS-stimulated dendritic cells to promote the development of T-helper type 2-like lymphocytes - Possible implications for NOD2-associated Crohn's disease. Journal of Crohn's & colitis, 1(2), 106-15. https://doi.org/10.1016/j.crohns.2007.08.006
Butler, Matt, et al. "NOD2 activity modulates the phenotype of LPS-stimulated dendritic cells to promote the development of T-helper type 2-like lymphocytes - Possible implications for NOD2-associated Crohn's disease." Journal of Crohn's & colitis vol. 1,2 (2007): 106-15. doi: https://doi.org/10.1016/j.crohns.2007.08.006
Butler M, Chaudhary R, van Heel DA, Playford RJ, Ghosh S. NOD2 activity modulates the phenotype of LPS-stimulated dendritic cells to promote the development of T-helper type 2-like lymphocytes - Possible implications for NOD2-associated Crohn's disease. J Crohns Colitis. 2007 Dec;1(2):106-15. doi: 10.1016/j.crohns.2007.08.006. Epub 2007 Sep 27. PMID: 21172192.
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J Crohns Colitis. 2007 Dec;1(2):106-15. doi: 10.1016/j.crohns.2007.08.006. Epub 2007 Sep 27.

NOD2 activity modulates the phenotype of LPS-stimulated dendritic cells to promote the development of T-helper type 2-like lymphocytes - Possible implications for NOD2-associated Crohn's disease.

Journal of Crohn's & colitis

Matt Butler, Rakesh Chaudhary, David A van Heel, Raymond J Playford, Subrata Ghosh

Affiliations

  1. Department of Gastroenterology, Imperial College London, Faculty of Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.

PMID: 21172192 DOI: 10.1016/j.crohns.2007.08.006

Abstract

Sensing of commensal microorganisms via Toll-like receptors (TLR) in the gut is essential for maintaining intestinal homeostasis in healthy individuals. Conversely, Crohn's disease is characterised by an inappropriate T helper-type 1 (Th1)-mediated immune response towards these same microorganisms. NOD2 is expressed by dendritic cells (DC) and mediates responses to bacterial muramyl-dipeptides (MDP). Mutations in NOD2 (CARD15) have recently been associated with susceptibility to Crohn's disease although the underlying mechanisms have yet to be established. We investigated the functional outcome of NOD2 and TLR4-mediated activation in monocyte-derived DC from wild-type NOD2 healthy controls and NOD2 frame-shift mutation-carrying Crohn's disease patients. In wild-type DC, MDP acted synergistically with LPS to amplify inflammatory cytokine production, enhance co-stimulatory molecule expression, and produce DC that promoted the proliferation of naïve, allogeneic, CD4(+) T lymphocytes with a Th2-like cytokine profile. By contrast, DC carrying homozygous NOD2 mutations were unable to react to MDP, responded to LPS only, and promoted the development of Th1 cells. These results suggest activation of the NOD2 pathway in DC modulates their response to TLR agonists and regulates their ability to induce polarised Th1 responses. As a consequence, Crohn's disease patients with defective NOD2 may be predisposed to the generation of strongly polarised Th1 responses against common commensal microorganisms.

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