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https://www.arca.fiocruz.br/handle/icict/16774
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2030-01-01
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- IOC - Artigos de Periódicos [12776]
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MICRORNA-21 TARGETS THE VITAMIN D-DEPENDENT ANTIMICROBIAL PATHWAY IN LEPROSY
Author
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.
David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA.
David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA.
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.
David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA.
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.
University of California at Los Angeles. Department of Microbiology, Immunology and Molecular Genetics. CA, USA.
University of Southern California School of Medicine. Department of Dermatology,. Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
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.
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..
David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA.
David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA.
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.
David Geffen School of Medicine at University of California at Los Angeles. Department of Medicine. Division of Dermatology. CA, USA.
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.
University of California at Los Angeles. Department of Microbiology, Immunology and Molecular Genetics. CA, USA.
University of Southern California School of Medicine. Department of Dermatology,. Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
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.
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..
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.
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