MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy.
MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy.
复制标题
作者：
麻风病提供了一个研究人类免疫调节机制的模型，因为这种疾病形成了一个临床免疫谱。在此，我们鉴定了13种在进行性麻风瘤（L-lep）与自限性结核样（T-lep）疾病受试者病变中差异表达的miRNA。生物信息学分析揭示了L-lep特异性miRNA的显著富集，其优先靶向L-lep与T-lep病变中下调的关键免疫基因。L-lep病变中差异表达最大的miRNA hsa-mir-21在M.麻风病感染的单核细胞Hsa-mir-2/1通过下调Toll样受体2/1（TLR 2/1）诱导的CYP 27 B1和IL 1B以及上调IL-10，抑制维生素D依赖性抗菌肽CAMP和DEFB 4A的基因表达。相反，在M.麻风感染的单核细胞增强了CAMP和DEFB 4A的表达，并恢复了TLR 2/1介导的抗M.麻风病人因此，M.麻风病人上调hsa-mir-21靶向与免疫定位疾病形式相关的多个基因，提供了一种有效的机制来逃避维生素D依赖性抗微生物途径。
Leprosy provides a model to investigate mechanisms of immune regulation in humans, given that the disease forms a clinical-immunological spectrum. Here, we identified 13 miRNAs that were differentially expressed in the lesions of subjects with progressive lepromatous (L-lep) vs. 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 vs. T-lep lesions. The most differentially expressed miRNA in L-lep lesions, hsa-mir-21, was upregulated in M. leprae-infected monocytes. Hsa-mir-21, by downregulating toll-like receptor 2/1 (TLR2/1)-induced CYP27B1 and IL1B as well as upregulating IL-10, inhibited gene expression of the 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.
登录
查看更多内容
DOI：
10.4049/jimmunol.0803560
发表时间：
2009-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu TX;Munitz A;Rothenberg ME
通讯作者：
Rothenberg ME
影响因子：
30.3
作者：
Montoya D;Cruz D;Teles RM;Lee DJ;Ochoa MT;Krutzik SR;Chun R;Schenk M;Zhang X;Ferguson BG;Burdick AE;Sarno EN;Rea TH;Hewison M;Adams JS;Cheng G;Modlin RL
通讯作者：
Modlin RL
影响因子：
6.4
作者：
Roy, S;Frodsham, A;Hill, AVS
通讯作者：
Hill, AVS
影响因子：
56.9
作者：
Liu, PT;Stenger, S;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
56.9
作者：
SALGAME, P;ABRAMS, JS;BLOOM, BR
通讯作者：
BLOOM, BR