| Author | Liu, Philip T. | |
| Author | Wheelwright, Matthew | |
| Author | Teles, Rosane | |
| Author | Komisopoulou, Evangelia | |
| Author | Edfeldt, Kristina | |
| Author | Ferguson, Benjamin | |
| Author | Mehta, Manali D. | |
| Author | Vazirnia, Aria | |
| Author | Rea, Thomas H. | |
| Author | Sarno, Euzenir N. | |
| Author | Graeber, Thomas G. | |
| Author | Modlin, Robert L. | |
| Access date | 2017-01-10T12:18:30Z | |
| Available date | 2017-01-10T12:18:30Z | |
| Document date | 2012 | |
| Citation | LIU, Philip T. et al. MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy. Nat Med., v.18, n.2, p.267-273, Aug. 2012. | pt_BR |
| ISSN | 1078-8956 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/16774 | |
| Language | eng | pt_BR |
| Publisher | Nature Publishing Group | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Hanseníase | pt_BR |
| Subject in Portuguese | MicroRNAs | pt_BR |
| Title | MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy | pt_BR |
| Type | Article | |
| DOI | 10.1038/nm.2584 | |
| Abstract | Leprosy provides a model to investigate mechanisms of immune regulation in humans, given that the disease forms a spectrum of clinical presentations that correlate with host immune responses. Here we identified 13 miRNAs that were differentially expressed in the lesions of subjects with progressive lepromatous (L-lep) versus the self-limited tuberculoid (T-lep) disease. Bioinformatic analysis revealed a significant enrichment of L-lep-specific miRNAs that preferentially target key immune genes downregulated in L-lep versus T-lep lesions. The most differentially expressed miRNA in L-lep lesions, hsa-mir-21, was upregulated in Mycobacterium leprae-infected monocytes. By directly downregulating Toll-like receptor 2/1 heterodimer (TLR2/1)-induced CYP27B1 and IL1B expression as well as indirectly upregulating interleukin-10 (IL-10), hsa-mir-21 inhibited expression of the genes encoding two vitamin D-dependent antimicrobial peptides, CAMP and DEFB4A. Conversely, knockdown of hsa-mir-21 in M. leprae-infected monocytes enhanced expression of CAMP and DEFB4A and restored TLR2/1-mediated antimicrobial activity against M. leprae. Therefore, the ability of M. leprae to upregulate hsa-mir-21 targets multiple genes associated with the immunologically localized disease form, providing an effective mechanism to escape from the vitamin D-dependent antimicrobial pathway. | pt_BR |
| Affilliation | University of California at Los Angeles. Orthopaedic Hospital Research Center. Los Angeles, CA, USA / David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA. | pt_BR |
| Affilliation | David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA. | pt_BR |
| Affilliation | David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA. | pt_BR |
| Affilliation | Crump Institute for Molecular Imaging. Institute for Molecular Medicine. Jonsson Comprehensive Cancer Center. California NanoSystems Institute. CA, USA / University of California. Department of Molecular and Medical Pharmacology. Los Angeles, CA, USA. | pt_BR |
| Affilliation | David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA. | pt_BR |
| Affilliation | David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA. | pt_BR |
| Affilliation | University of California at Los Angeles. Department of Microbiology, Immunology and Molecular Genetics. CA, USA. | pt_BR |
| Affilliation | University of California at Los Angeles. Department of Microbiology, Immunology and Molecular Genetics. CA, USA. | pt_BR |
| Affilliation | University of Southern California School of Medicine. Department of Dermatology,. Los Angeles, CA, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Crump Institute for Molecular Imaging. Institute for Molecular Medicine. Jonsson Comprehensive Cancer Center. California NanoSystems Institute. CA, USA / University of California. Department of Molecular and Medical Pharmacology. Los Angeles, CA, USA. | pt_BR |
| Affilliation | David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA / University of California at Los Angeles. Department of Microbiology, Immunology and Molecular Genetics. CA, USA.. | pt_BR |
| Subject | Leprosy | pt_BR |
| Subject | MicroRNA-21 | pt_BR |
| Subject | vitamin D-dependent | pt_BR |
| Subject | antimicrobial pathway | pt_BR |
| e-ISSN | 1546-170X | |
| Embargo date | 2030-01-01 | |
