IL-10 regulates Aicda expression through miR-155
Kirsten A Fairfax, Michael P Gantier, Fabienne Mackay, Bryan RG Williams, Claire E McCoy
JOURNAL OF LEUKOCYTE BIOLOGY | FEDERATION AMER SOC EXP BIOL | Published : 2015
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 B..View full abstract
Awarded by NHMRC
Awarded by Marie Curie Foundation
This work was made possible through the Victorian State Government Operational Infrastructure Support Program and the Australian Government National Health and Medical Research Council (NHMRC) Independent Research Institutes Infrastructure Support Scheme (IRIISS). This work was supported by grants from the NHMRC (Fellowship 516786 to K.A.F.; Project Grant 1022144 to M.P.G.; and Project Grant 1062683 to M.P.G. and B.R.G.W.) and the Health Research Board Ireland and Marie Curie Foundations (Fellowship MCPD/2009/2 to C.E.M.). The authors thank the facilities of our respective institutes, particularly those responsible for animal husbandry, and Frances Cribbin for assistance in preparing the manuscript.