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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3257-3265. Prepublished online as a Blood First Edition Paper on December 12, 2007; DOI 10.1182/blood-2007-06-096081. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-06-096081v1 111/6/3257    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jasperson, L. K Articles by Blazar, B. R Search for Related Content PubMed PubMed Citation Articles by Jasperson, L. K Articles by Blazar, B. R Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 15, 2007 Accepted November 17, 2007 Indoleamine 2,3-dioxygenase is a critical regulator of acute GVHD lethality Lisa K Jasperson, Christoph Bucher, Angela Panoskaltsis-Mortari, Patricia A Taylor, Andrew L Mellor, David H Munn, and Bruce R Blazar* Cancer Center and Department of Pediatrics, Division of BMT, University of Minnesota, Minneapolis, MN, United States Immunotherapy Center, Medical College of Georgia, Augusta, GA, United States * Corresponding author; email: blaza001{at}umn.edu. Graft versus host disease (GVHD) is initiated following activation of donor T cells by host antigen presenting cells (APCs). The immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) is expressed by APCs and parenchymal cells and is further inducible by inflammation. We investigated whether lethal conditioning and GVHD induce IDO and if IDO prevents tissue injury by suppressing immune responses at the induction site. We determined IDO is a critical regulator of GVHD, most strikingly in the colon, where epithelial cells dramatically upregulated IDO expression during GVHD. IDO-/- mice died more quickly from GVHD, displaying increased colonic inflammation and T cell infiltration. GVHD protection was not mediated by control of T cell proliferation, apoptosis, or effector mechanisms in lymphoid organs, nor did it require donor T regulatory cells (Tregs). Instead, T cells in IDO-/- colons underwent increased proliferation and decreased apoptosis compared to their wild-type counterparts. This evidence suggests IDO can act at the site of expression to decrease T cell proliferation and survival, diminishing colonic inflammation and reducing disease severity. These studies are the first to identify a function for IDO in GVHD lethality and indicate modulation of the IDO pathway may be an effective strategy for treatment of this disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: More ADO about IDO: GVHD Antonio Curti, Sara Trabanelli, and Roberto M. Lemoli Blood 2008 111: 2950. [Full Text] [PDF] This article has been cited by other articles: G. Socie and B. R. Blazar Acute graft-versus-host disease: from the bench to the bedside Blood, November 12, 2009; 114(20): 4327 - 4336. [Abstract] [Full Text] [PDF] A. Curti, S. Trabanelli, V. Salvestrini, M. Baccarani, and R. M. Lemoli The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology Blood, March 12, 2009; 113(11): 2394 - 2401. [Abstract] [Full Text] [PDF]

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