MicroRNAs (miRNAs) are expressed by cells that constitute the immune system, and they function by repressing specific mRNA targets at the post-transcriptional level.
The biosynthesis of miRNAs involves several levels of regulation, some of which are influenced by inflammation.
Specific miRNAs modulate haematopoietic cell development.
miRNAs regulate both innate and adaptive immune responses.
miRNA expression levels are dysregulated in diseases of immunological origin, such as cancer and autoimmunity. Altered miRNA expression can subsequently exacerbate disease severity.
Research into miRNA is a recent development, and therefore many aspects of miRNA biology remain unexplored.
Mammalian microRNAs (miRNAs) have recently been identified as important regulators of gene expression, and they function by repressing specific target genes at the post-transcriptional level. Now, studies of miRNAs are resolving some unsolved issues in immunology. Recent studies have shown that miRNAs have unique expression profiles in cells of the innate and adaptive immune systems and have pivotal roles in the regulation of both cell development and function. Furthermore, when miRNAs are aberrantly expressed they can contribute to pathological conditions involving the immune system, such as cancer and autoimmunity; they have also been shown to be useful as diagnostic and prognostic indicators of disease type and severity. This Review discusses recent advances in our understanding of both the intended functions of miRNAs in managing immune cell biology and their pathological roles when their expression is dysregulated.
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The writing of this review was supported by the United States National Institutes of Health (US NIH)(D.B), the Irvington Institute Fellowship Program of the Cancer Research Institute (R.M.O'C.), the US NIH 1K08CA133521 (D.S.R.) and the Graduate Research Fellowship Program of the National Science Foundation (A.A.C.).
D.B. is a director and Chair of the Scientific Advisory Board of Regulus, a company devoted to microRNA therapeutics. R.M.O'C. has consulted for Regulus. D.S.R. and A.A.C. have no competing financial interests.
- 3′ untranslated region
The sequence of a messenger RNA that is located downstream of the stop codon.
- RNA-induced silencing complex
A multicomponent ribonucleoprotein complex, comprising miRNAs or siRNAs and Argonaute proteins, that silences the expression of proteins from target mRNAs by cleavage or other unknown mechanisms depending on the complementarity of mRNA sequences to the packaged small RNAs.
- Processing bodies
Cytoplasmic foci that are thought to store and degrade translationally repressed RNA.
A tumour suppressor protein that is mutated in ∼50% of all human cancers. The p53 protein is a transcription factor that is activated by DNA damage, anoxia, expression of certain oncogenes and several other stress stimuli. Target genes activated by p53 regulate cell cycle arrest, apoptosis, cell senescence and DNA repair.
- Retinoic acid-inducible gene I
A cytoplasmic pathogen sensor that recognizes viral double-stranded RNA molecules and triggers an antiviral response.
- Germinal centre
A lymphoid structure that arises within follicles after immunization with, or exposure to, a T cell-dependent antigen. It is specialized for facilitating the development of high-affinity, long-lived plasma cells and memory B cells.
- Affinity maturation
The somatic mutation process by which B cells are selected for survival and proliferation on the basis of their increased affinity for antigen.
- Class switching
The somatic recombination process by which the class of immunoglobulin is switched from IgM to IgG, IgA or IgE.
- Regulatory T (TReg) cells
A small population of CD4+ T cells that naturally express high levels of CD25 (the interleukin-2 receptor α-chain) and FOXP3. They have suppressive regulatory activity towards other T cells that are stimulated through their T cell receptor. An absence of TReg cells or their dysfunction is associated with severe autoimmunity.
- V(D)J recombination
Somatic rearrangement of variable (V), diversity (D) and joining (J) regions of the genes that encode antigen receptors, leading to repertoire diversity of both T cell and B cell receptors.
- B-1 B cells
A subset of self-renewing B cells found mainly in the peritoneal cavity and the pleural cavity. They recognize self components, as well as common bacterial antigens, and they secrete antibodies that generally have low affinity and broad specificity.
- B-2 B cells
Conventional B cells. These cells reside in secondary lymphoid organs and secrete antibodies with high affinity and narrow specificity.
- RAG proteins
RAG1 and RAG2 are proteins that mediate V(D)J recombination in preB cells and thymocytes, which allows the production of antibodies and T cell receptors, respectively.
- Activation-induced cytidine deaminase
(AID). An RNA-editing enzyme that is necessary for antibody affinity maturation and class switching.
- Fragile site
A site in a chromosome that is susceptible to chromosome breakage and fusion with other chromosomes.
- Epigenetic regulation
The alteration of gene expression through transcriptional mechanisms (owing to promoter methylation) or post-transcriptional mechanisms instead of 'genetic' alteration of sequences of bases in genomic DNA.
The fusion protein that is generated by the t(8;21) translocation found in some acute myeloid leukaemias.
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O'Connell, R., Rao, D., Chaudhuri, A. et al. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 10, 111–122 (2010). https://doi.org/10.1038/nri2708
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