MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development.
Mammalian noncoding microRNAs (miRNAs) are a class of gene regulators that have been linked to immune system function. Here, we have investigated the role of miR-155 during an autoimmune inflammatory disease. Consistent with a positive role for miR-155 in mediating inflammatory responses, Mir155(-/-) mice were highly resistant to experimental autoimmune encephalomyelitis (EAE). miR-155 functions in the hematopoietic compartment to promote the development of inflammatory T cells including the T helper 17 (Th17) cell and Th1 cell subsets. Furthermore, the major contribution of miR-155 to EAE was CD4(+) T cell intrinsic, whereas miR-155 was also required for optimum dendritic cell production of cytokines that promoted Th17 cell formation. Our study shows that one aspect of miR-155 function is the promotion of T cell-dependent tissue inflammation, suggesting that miR-155 might be a promising therapeutic target for the treatment of autoimmune disorders.
O'Connell
Ryan M
RM
Division of Biology, California Institute of Technology, 330 Braun, 1200 E. California Boulevard, Pasadena, CA 91125, USA.
Kahn
Daniel
D
Gibson
William S J
WS
Round
June L
JL
Scholz
Rebecca L
RL
Chaudhuri
Aadel A
AA
Kahn
Melissa E
ME
Rao
Dinesh S
DS
Baltimore
David
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology; D020381:Interleukin-17 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology
D006023:Glycoproteins; D020381:Interleukin-17; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma