Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 5315K) PDF+supp data (7249K) PPT slides of all figures Supplemental Material Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Penack, O. Articles by van den Brink, M. R.M. PubMed PubMed Citation Articles by Penack, O. Articles by van den Brink, M. R.M. Social Bookmarking                            What's this?

¹ Department of Immunology and ² Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
³ Department of Hematology and Oncology, Charité, Campus Benjamin Franklin, Berlin 12200, Germany
⁴ Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065
⁵ Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610
⁶ Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115

CORRESPONDENCE Marcel R.M. van den Brink: m-van-den-brink{at}ski.mskcc.org

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.

Abbreviations used: allo-BMT, allogenic BM transplantation; allo-HSCT, allogeneic hematopoietic stem cell transplantation; AML, acute myeloid leukemia; GVHD, graft-versus-host disease; MDP, muramyl dipeptide; MLN, mesenteric LN; MLR, mixed leukocyte reaction; NOD2, nucleotide-binding oligomerization domain 2; SNP, single nucleotide polymorphism; TCD-BM, T cell–depleted BM; TLR, toll-like receptor.

© 2009 Penack et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS