Micro<scp>RNA</scp>s affect dendritic cell function and phenotype

Smyth, Lesley A.; Boardman, Dominic A.; Tung, Sim L.; Lechler, Robert I.; Lombardi, Giovanna

doi:10.1111/imm.12390

Cited by 98 publications

(104 citation statements)

References 88 publications

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“…Accumulating evidence highlights the importance of specific miRNAs in DC development, antigen presentation capacity, and cytokine release [39] . miR 146a [40] , miR155 [41] , and let7i [42] are involved in the maturation and functional state of DCs, while miR148/152 [43] and miR223 [44] are involved in their antigenpresentation capacity.…”

Section: Mirnas and Dcsmentioning

confidence: 99%

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

Zhang

2016

WJG

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Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. miRNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3′-untranslated region of specific mRNAs for degradation or translational inhibition. miRNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of miRNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how miRNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific miRNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing miRNAs as new biomarkers and as potential therapeutic targets in IBD.

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Section: Mirnas and Dcsmentioning

confidence: 99%

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

Zhang

2016

WJG

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“…Increasing evidences have revealed the critical role of miRs in regulating DC differentiation and function (40). For example, the overexpression of miR-146a or miR-142 inhibited the maturation and cytokine production of conventional DCs (41,42), whereas miR-23 and miR-10 induced tolerogenic properties of DCs (43,44).…”

Section: Discussionmentioning

confidence: 99%

Integrated Nanovaccine with MicroRNA-148a Inhibition Reprograms Tumor-Associated Dendritic Cells by Modulating miR-148a/DNMT1/SOCS1 Axis

Liu

et al. 2016

The Journal of Immunology

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Immunosuppressive tumor-associated dendritic cells (TADCs) are potential targets for cancer therapy. However, their poor responsiveness to TLR stimulation is a major obstacle for achieving successful cancer immunotherapy. In the current study, we reported a dysregulated miR-148a/DNA methyltransferase (DNMT)1/suppressor of cytokine signaling (SOCS)1 axis as a unique mechanism for dampened TLR stimulation in TADCs. The results showed that aberrantly elevated miR-148a in bone marrow–derived TADC (BM-TADC) abolished polyinosinic-polycytidylic acid (poly I:C) or LPS-induced dendritic cell maturation through directly suppressing DNMT1 gene, which consequently led to the hypomethylation and upregulation of SOCS1, the suppressor of TLR signaling. In contrast, miR-148a inhibitor (miR-148ai) effectively rescued the expression of DNMT1 and decreased SOCS1 in BM-TADCs, thereby recovering their sensitivity to TLR3 or TLR4 stimulation. To further reprogram TADCs in vivo, miR-148ai was coencapsulated with poly I:C and OVA by cationic polypeptide micelles to generate integrated polypeptide micelle/poly I:C (PMP)/OVA/148ai nanovaccine, which was designed to simultaneously inhibit miR-148a and activate TLR3 signaling in TADCs. The immunization of PMP/OVA/148ai nanovaccine not only effectively modulated the miR-148a/DNMT1/SOCS1 axis in the spleen, but also significantly increased mature dendritic cells both in the spleen and in tumor microenvironment. Moreover, PMP/OVA/148ai ameliorated tumor immunosuppression through reducing regulatory T cells and myeloid-derived suppressor cells, thereby leading to potent anticancer immune responses and robust tumor regression with prolonged survival. This study proposes a nanovaccine-based immunogene therapy with the integration of miR-148a inhibition and TLR3 stimulation as a novel therapeutic approach to boost anticancer immunity by reprogramming TADCs in vivo.

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“…Повышение экспрессии этой микроРНК также ассоциируется с активацией дендритных клеток. Предполагается, что miR-155 обладает способностью модулировать антиген-презентирующую активность дендрит-ных клеток (ДК), что приводит к активации Т-кле-ток [39]. Было отмечено, что в дендритных клетках, полученных из моноцитов человека, после актива-ции липополисахаридами экспрессия miR-155 по-вышалась более чем в 50 раз.…”

Section: микрорнк при остром клеточном отторжении трансплантированногunclassified

MicroRNAs in heart transplant recipients

Великий

Гичкун

Шевченко

2017

RJTAO

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1 ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, Москва, Российская Федерация 2 ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский университет), Москва, Российская Федерация Представлен анализ данных, посвященных прогностической роли микроРНК при отторжении трансплан-тированного сердца. МикроРНК представляют собой класс малых некодирующих РНК, регулирующих экспрессию генов и влияющих на различные клеточные функции. Отмечены изменения их профилей при различных патологических процессах и отторжении солидных органов. Предположительно измерение уровней микроРНК при трансплантации сердца может иметь диагностическое и прогностическое значе-ние при оценке риска развития отторжения и возможности минимизации иммуносупрессивной терапии. В настоящее время клинических данных о роли этих биомаркеров при трансплантации сердца накоплено недостаточно, и необходимы дальнейшие исследования связи уровней микроРНК с различными клини-ческими и лабораторными показателями у реципиентов сердца.Ключевые слова: микроРНК, трансплантация сердца, отторжение, васкулопатия.

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MicroRNAs affect dendritic cell function and phenotype

Cited by 98 publications

References 88 publications

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

Integrated Nanovaccine with MicroRNA-148a Inhibition Reprograms Tumor-Associated Dendritic Cells by Modulating miR-148a/DNMT1/SOCS1 Axis

MicroRNAs in heart transplant recipients

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