Blood Journal
Leading the way in experimental and clinical research in hematology

Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors

  1. Olaf Penack1,2,
  2. Ernst Holler3, and
  3. Marcel R. M. van den Brink2
  1. 1Department of Hematology and Oncology, Charité, Campus Benjamin Franklin, Berlin, Germany;
  2. 2Departments of Immunology and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and
  3. 3Department of Hematology/Oncology, University Medical Center, Regensburg, Germany

Abstract

Acute graft-versus-host disease (GVHD) remains the major obstacle to a more favorable therapeutic outcome of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized by tissue damage in gut, liver, and skin, caused by donor T cells that are critical for antitumor and antimicrobial immunity after HSCT. One obstacle in combating GVHD used to be the lack of understanding the molecular mechanisms that are involved in the initiation phase of this syndrome. Recent research has demonstrated that interactions between microbial-associated molecules (pathogen-associated molecular patterns [PAMPs]) and innate immune receptors (pathogen recognition receptors [PRRs]), such as NOD-like receptors (NLRs) and Toll-like receptors (TLRs), control adaptive immune responses in inflammatory disorders. Polymorphisms of the genes encoding NOD2 and TLR4 are associated with a higher incidence of GVHD in HSC transplant recipients. Interestingly, NOD2 regulates GVHD through its inhibitory effect on antigen-presenting cell (APC) function. These insights identify important mechanisms regarding the induction of GVHD through the interplay of microbial molecules and innate immunity, thus opening a new area for future therapeutic approaches. This review covers current knowledge of the role of PAMPs and PRRs in the control of adaptive immune responses during inflammatory diseases, particularly GVHD.

  • Submitted September 10, 2009.
  • Accepted December 8, 2009.
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