Faculty Collaboration Database

Regulation of acute graft-versus-host disease by microRNA-155. Blood 2012 May 17;119(20):4786-97

Date

03/13/2012

Pubmed ID

22408260

Pubmed Central ID

PMC3367879

DOI

10.1182/blood-2011-10-387522

Scopus ID

2-s2.0-84861209261 (requires institutional sign-in at Scopus site)   123 Citations

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.

Author List

Ranganathan P, Heaphy CE, Costinean S, Stauffer N, Na C, Hamadani M, Santhanam R, Mao C, Taylor PA, Sandhu S, He G, Shana'ah A, Nuovo GJ, Lagana A, Cascione L, Obad S, Broom O, Kauppinen S, Byrd JC, Caligiuri M, Perrotti D, Hadley GA, Marcucci G, Devine SM, Blazar BR, Croce CM, Garzon R

Author

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Animals
Cells, Cultured
Female
Gene Expression Regulation
Genetic Therapy
Graft vs Host Disease
Humans
Lymphocyte Activation
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
MicroRNAs
Spleen
T-Lymphocytes