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MicroRNA-155 Promotes Autoimmune Inflammation by Enhancing Inflammatory T Cell Development

O'Connell, Ryan M. and Kahn, Daniel A. and Gibson, William S. J. and Round, June L. and Scholz, Rebecca L. and Chaudhuri, Aadel A. and Kahn, Melissa E. and Rao, Dinesh S. and Baltimore, David (2010) MicroRNA-155 Promotes Autoimmune Inflammation by Enhancing Inflammatory T Cell Development. Immunity, 33 (4). pp. 607-619. ISSN 1074-7613. PMCID PMC2966521. https://resolver.caltech.edu/CaltechAUTHORS:20101213-114734795

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.immuni.2010.09.009 DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2966521PubMed CentralArticle
ORCID:
AuthorORCID
Rao, Dinesh S.0000-0002-0794-9337
Baltimore, David0000-0001-8723-8190
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.
Funders:
Funding AgencyGrant Number
Cancer Research InstituteUNSPECIFIED
NIHK99HL102228
NIHK12 HD001400
NSFUNSPECIFIED
NIH1K08CA133521
NIH1R01A1079243 01
Jane Coffin Child's Memorial FundUNSPECIFIED
National Cancer InstituteUNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC2966521
Record Number:CaltechAUTHORS:20101213-114734795
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20101213-114734795
Official Citation:Ryan M. O'Connell, Daniel Kahn, William S.J. Gibson, June L. Round, Rebecca L. Scholz, Aadel A. Chaudhuri, Melissa E. Kahn, Dinesh S. Rao, David Baltimore, MicroRNA-155 Promotes Autoimmune Inflammation by Enhancing Inflammatory T Cell Development, Immunity, Volume 33, Issue 4, 2010, Pages 607-619, ISSN 1074-7613, https://doi.org/10.1016/j.immuni.2010.09.009. (http://www.sciencedirect.com/science/article/pii/S1074761310003511)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:21328
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 Dec 2010 20:41
Last Modified:21 Apr 2020 21:30

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