NOD2 regulates hematopoietic cell function during graft-versus-host disease Journal Article
| Authors: | Penack, O.; Smith, O. M.; Cunningham-Bussel, A.; Liu, X.; Rao, U.; Yim, N.; Na, I. K.; Holland, A. M.; Ghosh, A.; Lu, S. X.; Jenq, R. R.; Liu, C.; Murphy, G. F.; Brandl, K.; van den Brink, M. R. M. |
| Article Title: | NOD2 regulates hematopoietic cell function during graft-versus-host disease |
| 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<sup>-/-</sup> 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. © 2009 Penack et al. |
| Keywords: | controlled study; single nucleotide polymorphism; genetics; polymorphism, single nucleotide; nonhuman; protein function; lymphocyte proliferation; t lymphocyte; animal cell; mouse; animal; cytology; animals; mice; animal experiment; animal model; allogenic bone marrow transplantation; mice, inbred balb c; physiology; chimera; disease model; immunology; lymphocyte activation; bagg albino mouse; hematopoietic system; graft versus host reaction; hematopoietic cell; neoplasms, experimental; colitis; experimental neoplasm; mice, inbred nod; bone marrow transplantation; graft vs host disease; nonobese diabetic mouse; antigen presenting cell; antigen-presenting cells; caspase recruitment domain protein 15; card15 protein, mouse; nod2 signaling adaptor protein |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 206 |
| Issue: | 10 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2009-09-28 |
| Start Page: | 2101 |
| End Page: | 2110 |
| Language: | English |
| DOI: | 10.1084/jem.20090623 |
| PUBMED: | 19737867 |
| PROVIDER: | scopus |
| PMCID: | PMC2757869 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 30 November 2010" - "CODEN: JEMEA" - "Source: Scopus" |
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