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MiR-182 is largely dispensable for adaptive immunity: lack of correlation between expression and function.

ABSTRACT: MicroRNA (miR)-mediated regulation of protein abundance is a pervasive mechanism of directing cellular processes. The well-studied and abundant miR-182 has previously been implicated in many aspects of T cell function, DNA repair, and cancer. In this study, we show that miR-182 is the most highly induced miR in B cells undergoing class-switch recombination. To elucidate the requirement of miR-182 in lymphocyte function, we extensively characterized mice with a targeted deletion of Mir182. We show that despite its dramatic induction, loss of miR-182 has minimal impact on B cell development, the ability of B cells to undergo class-switch recombination ex vivo and to undergo Ag-driven affinity maturation in vivo. Furthermore, in striking contrast to knockdown studies that demonstrated the requirement of miR-182 in T cell function, miR-182-deficient mice display no defect in T cell development and activation. Finally, we show that T cell-dependent immune response to experimental Listeria monocytogenes infection is intact in miR-182-deficient mice. We conclude that, contrary to previous studies, miR-182 does not play a significant role in all measured aspects of mouse adaptive immunity. This striking absence of a phenotype highlights the lack of correlation between expression pattern and functional requirement, underscores the limitations of using knockdown approaches to assess miR requirements, and suggests that miR networks may compensate for the chronic loss of specific miRs.

SUBMITTER: Pucella JN

PROVIDER: S-EPMC4355037 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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miR-182 is largely dispensable for adaptive immunity: lack of correlation between expression and function.

Pucella Joseph N JN Yen Wei-Feng WF Kim Myoungjoo V MV van der Veeken Joris J Luo Chong T CT Socci Nicholas D ND Naito Yukiko Y Li Ming O MO Iwai Naoharu N Chaudhuri Jayanta J

Journal of immunology (Baltimore, Md. : 1950) 20150211 6

MicroRNA (miR)-mediated regulation of protein abundance is a pervasive mechanism of directing cellular processes. The well-studied and abundant miR-182 has previously been implicated in many aspects of T cell function, DNA repair, and cancer. In this study, we show that miR-182 is the most highly induced miR in B cells undergoing class-switch recombination. To elucidate the requirement of miR-182 in lymphocyte function, we extensively characterized mice with a targeted deletion of Mir182. We sho ...[more]

PMID: 25672759

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Project description:The relationship between miR-21 and miR-182 gene expression in peripheral blood and gastric cancer tissue was investigated, exploring the relationship between the levels of miR-21 and miR-182 and prognosis of gastric cancer patients, and determining the effects of these two genes on the growth and migration of gastric cancer cells. Fifty gastric cancer patients who were treated in the 254th Hospital of PLA, from July 2012 to July 2014 were selected. Peripheral blood samples were drawn from patients, and 50 healthy subjects were studied as controls. The levels of the miR-21 and miR-182 genes were detected by semi-quantitative PCR, and the correlation between miR-21 and miR-182 expression and clinicopathological features was explored. Moreover, the effects of miR-21 and miR-182 expression on the survival time and prognosis of patients were investigated. siRNA was used to downregulate miR-21 and miR-182 gene expression in MGC-803 gastric cancer cells, and MTT and Transwell assays were conducted. As a result, the relative expression levels of miR-21 and miR-182 in peripheral blood of gastric cancer patients were significantly higher than in healthy subjects (p<0.01) and the relative expression of miR-182 was closely related to the clinicopathological features of gastric cancer patients (p<0.05); high expression of miR-21 and miR-182 was associated with reduced survival time of patients (p<0.05); MGC-803 cells with low expression of miR-21 and miR-182 were analyzed, showing that miR-182 promoted cell proliferation and migration (p<0.01). In conclusion, the relative levels of miR-21 and miR-182 in peripheral blood of patients with gastric cancer are significantly increased; low expression of miR-182 can significantly reduce the proliferation and migration of gastric cancer cells. Moreover, miR-182 expression, which is closely related to the clinicopathological features of gastric cancer, can serve as a target for the clinical treatment of gastric cancer.

Project description:BackgroundHow far the role of innate immunity and adaptive immunity do in children who have been BCG vaccinated in controlling the course and the severity of the TB disease has not been completely known. Mycobacterium tuberculosis entry to the body will be recognized by Toll-like receptors found on macrophages, neutrophils, and dendritic cells as part of the innate immune response, after which the dendritic cells will then present the antigen to lymphocyte T0 cells and initiate the adaptive immune response (of which CD4 T cells have an important role in). Was one or were both of these immune responses function well or not in a BCG Vaccinated Children with TB?ObjectiveThis study aim to find a better understanding of the role of innate immune response assessed by TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels, while the role of adaptive immune response is assessed by analyzing serum CD4 level in children with TB who have had BCG vaccination.MethodsThis cross-sectional study was conducted among children with TB at the outpatient and inpatient wards at Bhakti Medicare and Jakarta Islamic Hospital. Expression of mRNA gene was measured using the Boom method and protein serum levels were measured using the ELISA method. The results were analyzed by using the SPSS v.23 program.ResultsSixty-nine children were recruited as subjects. In this study, 68.1% of whom had BCG scars. TLR4 mRNA gene expression was found to be higher than TLR2 mRNA gene expression. Serum CD4 level was found to be highest out of TLR2 and TLR4 level, but serum TLR2 level was higher than TLR4 level. TLR2/TLR4 mRNA gene expression, serum TLR2/TLR4 levels, and CD4 levels in subjects with BCG scar were also found to be significantly higher than in subjects without BCG scar (p < 0.001). There was a significant positive correlation between TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels (r = 0.860; r = 0.864; p < 0.001) and between serum levels TLR2/TLR4 with serum CD4 levels (r = 0.822; r = 0.832 p < 0.001).ConclusionAs early as possible, BCG vaccine administration is needed in endemic countries, but it must be ensured that scars can be formed. It is also important to control Latent TB Infection (LTBI) to prevent transmission and relapse of disease.

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MiR-182 is largely dispensable for adaptive immunity: lack of correlation between expression and function.

Publications

miR-182 is largely dispensable for adaptive immunity: lack of correlation between expression and function.

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