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NOD2 regulates hematopoietic cell function during graft-versus-host disease

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Item Type:Article
Title:NOD2 regulates hematopoietic cell function during graft-versus-host disease
Creators Name:Penack, O. and Smith, O.M. and Cunningham-Bussel, A. and Liu, X. and Rao, U. and Yim, N. and Na, I.K. and Holland, A.M. and Ghosh, A. and Lu, S.X. and Jenq, R.R. and Liu, C. and Murphy, G.F. and Brandl, K. and van den Brink, M.R.M.
Abstract:Nucleotide-binding oligomerization domain 2 (NOD2) polymorphisms are independent risk factors for Crohn's disease and graft-versus-host disease (GVHD). In Crohn's disease, the proinflammatory state resulting from NOD2 mutations have been associated with a loss of antibacterial function of enterocytes such as paneth cells. NOD2 has not been studied in experimental allogeneic bone marrow transplantation (allo-BMT). Using chimeric recipients with NOD2(-/-) hematopoietic cells, we demonstrate that NOD2 deficiency in host hematopoietic cells exacerbates GVHD. We found that proliferation and activation of donor T cells was enhanced in NOD-deficient allo-BMT recipients, suggesting that NOD2 plays a role in the regulation of host antigen-presenting cells (APCs). Next, we used bone marrow chimeras in an experimental colitis model and observed again that NOD2 deficiency in the hematopoietic cells results in increased intestinal inflammation. We conclude that NOD2 regulates the development of GVHD through its inhibitory effect on host APC function.
Keywords:Antigen-Presenting Cells, Bone Marrow Transplantation/immunology, Colitis, Experimental Neoplasms, Graft vs Host Disease, Hematopoietic System, Lymphocyte Activation, Nod2 Signaling Adaptor Protein, Single Nucleotide Polymorphism, Animals, Mice
Source:Journal of Experimental Medicine
Publisher:Rockefeller University Press
Page Range:2101-2110
Date:28 September 2009
Official Publication:https://doi.org/10.1084/jem.20090623
PubMed:View item in PubMed

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