MicroRNA-155 Promotes Autoimmune Inflammation by Enhancing Inflammatory T Cell Development
Abstract
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.
Additional Information
© 2010 Elsevier Inc. Received 5 April 2010; revised 19 July 2010; accepted 13 September 2010. Published online: September 30, 2010. Available online 30 September 2010. R.M.O. was funded in part by the Irvington Institute Fellowship Program of the Cancer Research Institute and by award number K99HL102228 from the National Heart, Lung and Blood Institute. D.K. was supported by the National Institutes of Health—Building Interdisciplinary Research Careers in Women's Health (BIRCWH) center at UCLA (K12 HD001400). A.A.C. was funded by the Graduate Research Fellowship Program of the National Science Foundation. D.S.R. was funded by award number 1K08CA133521 from the National Cancer Institute. J.L.R. is a Merck Fellow of the Jane Coffin Child's Memorial Fund. This work was also supported by NIH grant 1R01AI079243-01. We would like to thank A. Bradley for providing us with Mir155/ animals. D.B. is a scientific advisor to Regulus Therapeutics, a company devoted to micro- RNA therapeutics.Attached Files
Accepted Version - nihms237810.pdf
Supplemental Material - OConnell2010p12127Immunity_supp.pdf
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Additional details
- PMCID
- PMC2966521
- Eprint ID
- 21328
- Resolver ID
- CaltechAUTHORS:20101213-114734795
- Cancer Research Institute
- NIH
- K99HL102228
- NIH
- K12 HD001400
- NSF
- NIH
- 1K08CA133521
- NIH
- 1R01A1079243 01
- Jane Coffin Child's Memorial Fund
- National Cancer Institute
- Created
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2010-12-14Created from EPrint's datestamp field
- Updated
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2021-11-09Created from EPrint's last_modified field