title: Regulation of acute graft-versus-host disease by microRNA-155.
abstract: Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic stem cell transplant (alloHSCT), underscoring the need to further elucidate its mechanisms and develop novel treatments. Based on recent observations that microRNA-155 (miR-155) is up-regulated during T-cell activation, we hypothesized that miR-155 is involved in the modulation of aGVHD. Here we show that miR-155 expression was up-regulated in T cells from mice developing aGVHD after alloHSCT. Mice receiving miR-155-deficient donor lymphocytes had markedly reduced lethal aGVHD, whereas lethal aGVHD developed rapidly in mice recipients of miR-155 overexpressing T cells. Blocking miR-155 expression using a synthetic anti-miR-155 after alloHSCT decreased aGVHD severity and prolonged survival in mice. Finally, miR-155 up-regulation was shown in specimens from patients with pathologic evidence of intestinal aGVHD. Altogether, our data indicate a role for miR-155 in the regulation of GVHD and point to miR-155 as a novel target for therapeutic intervention in this disease.
authors.affiliation: Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, Ohio State University, 460 West 12th Ave., Columbus, OH 43210, USA.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Ranganathan
authors.forename: Catherine E A
authors.initials: CE
authors.lastname: Heaphy
authors.forename: Stefan
authors.initials: S
authors.lastname: Costinean
authors.forename: Nicole
authors.initials: N
authors.lastname: Stauffer
authors.forename: Caroline
authors.initials: C
authors.lastname: Na
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Santhanam
authors.forename: Charlene
authors.initials: C
authors.lastname: Mao
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Taylor
authors.forename: Sukhinder
authors.initials: S
authors.lastname: Sandhu
authors.forename: Gang
authors.initials: G
authors.lastname: He
authors.forename: Arwa
authors.initials: A
authors.lastname: Shana'ah
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lagana
authors.forename: Luciano
authors.initials: L
authors.lastname: Cascione
authors.forename: Susanna
authors.initials: S
authors.lastname: Obad
authors.forename: Oliver
authors.initials: O
authors.lastname: Broom
authors.forename: Sakari
authors.initials: S
authors.lastname: Kauppinen
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Michael
authors.initials: M
authors.lastname: Caligiuri
authors.forename: Danilo
authors.initials: D
authors.lastname: Perrotti
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Hadley
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Ramiro
authors.initials: R
authors.lastname: Garzon
mesh_terms: D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D015316:Genetic Therapy; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse