biostudies-literatureLiu PTNIAID NIH HHSNIAMS NIH HHS267-73https://www.ebi.ac.uk/biostudies/studies/S-EPMC3274599biostudies-literatureUnknown18(2)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 indirectNature medicineMicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy.PMC3274599R01 AI022553AI 073539AI 047868R01 AI082575AR 040312K22 AI085025AI 022553R37 AI047868R01 AR040312K22 AI 85025R01 AI073539R01 AI047868Vazirnia ALiu PTSarno ENEdfeldt KKomisopoulou EModlin RLWheelwright MTeles RMehta MDGraeber TGFerguson BRea THfalseMicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy.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 indirect2012-01-01T00:00:00Z2012 Jan2026-04-28T22:11:28.687Z2026-04-07T14:42:31.341ZS-EPMC32745992228630510.1038/nm.2584