Work

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

Year: 2009

Type: article

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.

Source: The Journal of Experimental Medicine

DOI: 10.1084/jem.20090623

Authors: Olaf Penack, Odette M. Smith, Amy Cunningham-Bussel, Xin Liu, Uttam Rao, Nury Yim, Il-Kang Na, Amanda M. Holland, Arnab Ghosh, Sydney X. Lu, Robert R. Jenq, Chen Liu, George F. Murphy, Katharina Brandl, Marcel R.M. van den Brink

Institutions: Memorial Sloan Kettering Cancer Center, Stiftung Charité, Charité – Universitätsmedizin Berlin, Weill Cornell Medicine, University of Florida Health, University of Florida, Brigham and Women's Hospital, Harvard University

Language: English

Topic: Hematopoietic Stem Cell Transplantation

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Elsa U. Pardee Foundation, Commonwealth Foundation, Alexander von Humboldt-Stiftung, Memorial Sloan-Kettering Cancer Center, Emerald Foundation, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases

Awards: Targeted antigen receptor treatment of cancer, Strategies to Enhance Lymphoid Recovery After Radiation-Induced Injury, Strategies to enhance immune reconstitution after bone marrow transplant, T cell homing in intestinal graft-versus-host disease, Weill Cornell/Rockefeller/Sloan Kettering MST Program, G9000349575, Cancer Center Support Grant, Cellular Pathology of Graft Versus Host Disease

OpenAlex ID: W2105127697

FWCI: 9.075

Cites: 31

Cited by: 109

Related to: 10