IL-10 regulates Aicda expression through miR-155.
Aicda is a critical component of antibody class-switching in B cells. In this work, we study the impact of TLR4 activation and IL-10 stimulation on Aicda expression in B cells. Through the global analysis of miRNAs in response to TLR4 activation, in combination with IL-10 stimulation, we identified that IL-10 can suppress TLR4-induced miR-155 expression, an effect that resulted in enhanced Aicda expression. Furthermore, when preventing miR-155 control of Aicda expression, by genetic mutation of its target site in the Aicda mRNA, IL-10 could further potentiate Aicda expression. Given that miR-155 expression is lost, and expression levels of both Aicda and IL-10 are high in diseases, such as Burkitt's lymphoma, our results suggest a stringent and sophisticated control of Aicda by a novel IL-10/miR-155 axis, where the imbalance of IL-10 and/or miR-155 may contribute to disease pathogenesis.
*Faculty of Medicine, Department of Immunology, Monash University, Prahran, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia; The Department of Experimental Medicine, University of Melbourne, Parkville, Victoria, Australia; Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Centre for Cancer Research, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia; and School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
Kirsten A
KA
Fairfax
*Faculty of Medicine, Department of Immunology, Monash University, Prahran, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia; The Department of Experimental Medicine, University of Melbourne, Parkville, Victoria, Australia; Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Centre for Cancer Research, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia; and School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
Michael P
MP
Gantier
*Faculty of Medicine, Department of Immunology, Monash University, Prahran, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia; The Department of Experimental Medicine, University of Melbourne, Parkville, Victoria, Australia; Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Centre for Cancer Research, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia; and School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
Fabienne
F
Mackay
*Faculty of Medicine, Department of Immunology, Monash University, Prahran, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia; The Department of Experimental Medicine, University of Melbourne, Parkville, Victoria, Australia; Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Centre for Cancer Research, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia; and School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
Bryan R G
BR
Williams
*Faculty of Medicine, Department of Immunology, Monash University, Prahran, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia; The Department of Experimental Medicine, University of Melbourne, Parkville, Victoria, Australia; Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Centre for Cancer Research, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia; and School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland claire.mccoy@mimr-phi.org.
Claire E
CE
McCoy
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
C556062:IL10 protein, mouse; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016753:Interleukin-10; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
AID; B cell; TLR4; antibody class-switching; interleukin; miRNA