The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
MicroRNA-21 Limits In Vivo Immune Response-Mediated Activation of the IL-12/IFN-γ Pathway, Th1 Polarization, and the Severity of Delayed-Type Hypersensitivity
Open accessAbstract
An altered balance between Th1 and Th2 cytokines is responsible for a variety of immunoinflammatory disorders such as asthma, yet the role of posttranscriptional mechanisms, such as those mediated by microRNAs (miRs), in adjusting the relative magnitude and balance of Th cytokine expression have been largely unexplored. In this study, we show that miR-21 has a central role in setting a balance between Th1 and Th2 responses to Ags. Targeted ablation of miR-21 in mice led to reduced lung eosinophilia after allergen challenge, with a broadly reprogrammed immunoactivation transcriptome and significantly increased levels of the Th1 cytokine IFN-γ. Biological network-based transcriptome analysis of OVA-challenged miR-21−/− mice identified an unexpected prominent dysregulation of IL-12/IFN-γ pathways as the most significantly affected in the lungs, with a key role for miR-21 in IFN-γ signaling and T cell polarization, consistent with a functional miR-21 binding site in IL-12p35. In support of these hypotheses, miR-21 deficiency led dendritic cells to produce more IL-12 after LPS stimulation and OVA-challenged CD4+ T lymphocytes to produce increased IFN-γ and decreased IL-4. Further, loss of miR-21 significantly enhanced the Th1-associated delayed-type hypersensitivity cutaneous responses. Thus, our results define miR-21 as a major regulator of Th1 versus Th2 responses, defining a new mechanism for regulating polarized immunoinflammatory responses.
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Cites
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BackgroundCELLULAR RESPONSES TO INTERFERON-γ
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Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21
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Cited by
Turning 21: Induction of miR-21 as a Key Switch in the Inflammatory Response
Sheedy, F. J. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00019 · Cited by 496
Emerging role of microRNA-21 in cancer
Feng, Y.-H., & Tsao, C.-J. (2016) · Biomedical Reports · doi:10.3892/br.2016.747 · Cited by 454
MicroRNA-mediated regulation of T helper cell differentiation and plasticity
Baumjohann, D., & Ansel, K. M. (2013) · Nature Reviews Immunology · doi:10.1038/nri3494 · Cited by 360
Anti-Inflammatory MicroRNAs and Their Potential for Inflammatory Diseases Treatment
Tahamtan, A., Teymoori-Rad, M., Nakstad, B., & Salimi, V. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01377 · Cited by 357
Targeting cell signaling in allergic asthma
Athari, S. S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0079-0 · Cited by 312
Metadata
- Authors
- Lu, T. X., Hartner, J., Lim, E.-J., Fabry, V., Mingler, M. K., Cole, E. T., Orkin, S. H., Aronow, B. J., & Rothenberg, M. E.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-09
- Volume
- 187
- Issue
- 6
- Pages
- 3362-3373
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2118842534
- Cited by
- 341
- References
- 10
- FWCI
- 9.42
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: MicroRNA-21 Limits In Vivo Immune Response-Mediated Activation of the IL-12/IFN-γ Pathway, Th1 Polarization, and the Severity of Delayed-Type Hypersensitivity. https://app.cochat.ai/papers/10.4049/jimmunol.1101235
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- Lu, T. X., Hartner, J., Lim, E.-J., Fabry, V., Mingler, M. K., Cole, E. T., Orkin, S. H., Aronow, B. J., & Rothenberg, M. E. (2011). MicroRNA-21 Limits In Vivo Immune Response-Mediated Activation of the IL-12/IFN-γ Pathway, Th1 Polarization, and the Severity of Delayed-Type Hypersensitivity. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1101235
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