miR-182 is largely dispensable for adaptive immunity: Lack of correlation between expression and function Journal Article
| Authors: | Pucella, J. N.; Yen, W. F.; Kim, M. V.; Van Der Veeken, J.; Luo, C. T.; Socci, N. D.; Naito, Y.; Li, M. O.; Iwai, N.; Chaudhuri, J. |
| Article Title: | 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 wellstudied 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. Copyright © 2015 by The American Association of Immunologists, Inc. |
| Keywords: | protein expression; unclassified drug; gene deletion; nonhuman; binding affinity; animal cell; mouse; microrna; protein depletion; animal experiment; animal model; in vivo study; b lymphocyte; correlation analysis; cellular immunity; gene rearrangement; adaptive immunity; ex vivo study; t lymphocyte activation; listeriosis; lymphocyte function; male; priority journal; article; protein mir 182; mir182 gene |
| Journal Title: | Journal of Immunology |
| Volume: | 194 |
| Issue: | 6 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2015-03-15 |
| Start Page: | 2635 |
| End Page: | 2642 |
| Language: | English |
| DOI: | 10.4049/jimmunol.1402261 |
| PROVIDER: | scopus |
| PMCID: | PMC4355037 |
| PUBMED: | 25672759 |
| DOI/URL: | |
| Notes: | Correction issued, see DOI: 10.4049/jimmunol.1501331 -- Export Date: 2 April 2015 -- Source: Scopus |
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