MicroRNAs, The Immune System and Rheumatic Disease

Esmerina Tili; Jean-Jacques Michaille; Stefan Costinean; Carlo M. Croce

Disclosures

Nat Clin Pract Rheumatol. 2008;4(10):534-541. 

In This Article

Overview of miRNAs in Hematopoiesis and the Immune Response

Combined analyses of miRNA expression in hematopoietic lineages, using genome-wide microarray profiling along with the characterization of individual miRNAs by cloning, northern blotting and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), has resulted in the identification of miRNAs that are now considered as 'markers' of these lineages.[10,11,12,13,14,15,16]

The spectrum of miRNA expression is also known to change during lymphoid and myeloid maturation, as well as upon antigen recognition.[10,11,12,13,17] miRNA expression profiling in naive, effector and memory CD8+ T cells revealed the dynamic regulation of miRNAs during antigen-induced CD8+ T-cell differentiation.[17] The striking global downregulation of miRNAs in effector T cells, which are considered to be in a highly active state, mirrors the global miRNA downregulation associated with some cancers.[18] Cytokine stimulation of immune cells also leads to a rapid shift in miRNA levels. For example, miR-125b and miR-155 levels oscillate within an hour of tumor necrosis factor (TNF) stimulation in mouse Raw 264.7 cells.[14] These changes in miRNA levels enable the immune cells to limit the level and duration of immune responses to infections so that these responses do not become detrimental to the health of the organism. Rapid changes in the levels of several miRNAs, however, were reported in the hepatoma cell line Huh7 treated with interferon (IFN)-ß.[19] These rapid modifications of miRNA levels might, therefore, generally be required to overcome the inherent buffering properties of biological systems, thereby allowing cell transitions from one stage of differentiation to another.

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