Elena Vigorito
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• Recent, selected Publications

miRNA regulation of the immune system

MicroRNAs (miRNAs) are small endogenous RNA molecules that regulate gene expression by base-paring with target messenger RNAs (mRNAs), leading to mRNA degradation or translational repression. As a result, miRNAs control protein concentration at post-transcriptional and translational levels, but do not affect mRNA transcription or protein stability. Several thousand miRNAs have been identified in organisms as diverse as viruses, worms or mammals, and it is currently predicted that 10-30% of genes in humans might be regulated by miRNAs.

During the course of immune responses lymphocytes must respond rapidly to antigenic stimulation by initiating complex changes in gene expression that allow differentiation into effector and memory cells. These events lead to the production of high affinity antibodies and development of lasting immunological protection which underpins effective vaccination. Understanding lymphocyte function is therefore relevant for improving health, but also for treatment of diseases, as aberrant lymphocyte function leads to autoimmunity or cancer.

Our previous work has implicated a particular miRNA, miR-155, as being required for lymphocyte function (Science, 2007). Further studies in our laboratory have revealed that miR-155 is required for the production of high affinity antibodies by B cells. We have identified miR155 potential target genes which abnormal expression may contribute to the B and T cell phenotype. This knowledge may also be relevant for cancer biology as over-expression of miR-155 leads to B cell transformation. Only by understanding the normal biological processes regulated by miRNAs and their network of target genes will it be possible to safely unlock their full potential for pharmaceutical intervention in the treatment of human diseases.

Recent, selected publications

Rodriguez A*, Vigorito E*, Clare S, Warren MV, Couttet P, Soond DA, Van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A (2007) Requirement of bic/microRNA-155 for normal immune function.
Science 316 608-611 * Authors contributed equally
http://dx.doi.org/10.1126/science.1139253

Vigorito E, Kovesdi D, Turner M (2006) Synergistic activation of PKD by the B cell antigen receptor and CD19 requires PI3K, Vav1 and PLCγ.
Cellular Signalling 18 1455-1460
http://dx.doi.org/10.1016/j.cellsig.2005.11.008

Hebeis B*, Vigorito E*, Kovesdi D, Turner M (2005)
Vav proteins are required for B-lymphocyte responses to LPS.
Blood 106 635-640 * Authors contributed equally
http://dx.doi.org/10.1182/blood=2004-10-3919

Vigorito E, Gambardella L, Colucci F, McAdam S, Turner M (2005)
Vav proteins regulate peripheral B-cell survival.
Blood 106 2391-2398
http://dx.doi.org/10.1182/blood-2004-12-4894

Vigorito E, Bardi G, Glassford J, Lam EW-F, Clayton E, Turner M (2004) Vav-dependent and Vav-independent phosphatidylinositol 3-kinase activation in murine B cells determined by the nature of the stimulus.
Journal of Immunology 173 3209-3214
http://www.jimmunol.org/cgi/content/abstract/173/5/3209

Vigorito E, Clayton E, Turner M (2004) BCR activatation of PI3K is Vav-independent in murine B cells.
Biochemical Society Transactions 32 781-784
http://www.biochemsoctrans.org/bst/032/bst0320781.htm

Vigorito E, Bell S, Hebeis BJ, Reynolds H, McAdam S, Emson PC, McKenzie A, Turner M (2004) Immunological function in mice lacking the Rac-related GTPase RhoG.
Molecular and Cellular Biology 24 719-729
http://dx.doi.org/10.1128/MCB.24.2.719-729.2004

Johmura S, Oh-hora M, Inabe K, Nishikawa Y, Hayashi K, Vigorito E, Kitamura D, Turner M, Shingu K, Hikida M, Kurosaki T (2003) Regulation of Vav localization in membrane rafts by adaptor molecules Grb2 and BLNK.
Immunity 18 777-787
http://dx.doi.org/10.1016/S1074-7613(03)00139-0

Vigorito E, Billadeu DD, Savoy D, McAdam S, Doody G, Fort P, Turner M (2003) RhoG regulates gene expression and the actin cytoskeleton in lymphocytes.
Oncogene 22 330-342
http://dx.doi.org/10.1038/sj.onc.1206116

Clayton E, Bardi G, Bell SE, Chantry D, Downes CP, Gray A, Humphries LA, Rawlings D, Reynolds H, Vigorito E, Turner M (2002) A crucial role for the p110δ subunit of phosphatidylinositol 3-kinase in B cell development and activation.
Journal of Experimental Medicine 196 753-763
http://dx.doi.org/10.1084/jem.20020805

Doody GM, Bell SE, Vigorito E, Clayton E, McAdam S, Tooze R, Fernandez C, Lee IJ, Turner M (2001) Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation.
Nature Immunology 2 542-547
http://dx.doi.org/10.1038/88748