Journal article

IRF4 Activity Is Required in Established Plasma Cells to Regulate Gene Transcription and Mitochondrial Homeostasis

Michael Sze Yuan Low, Erica J Brodie, Pasquale L Fedele, Yang Liao, George Grigoriadis, Andreas Strasser, Axel Kallies, Simon N Willis, Julie Tellier, Wei Shi, Sarah Gabriel, Kristy O'Donnell, Catherine Pitt, Stephen L Nutt, David Tarlinton

Cell Reports | CELL PRESS | Published : 2019

Abstract

The transcription factor interferon regulatory factor 4 (IRF4) is critical for the development, maintenance, and function of plasma cells. The mechanism by which IRF4 exerts its action in mature plasma cells has been elusive due to the death of all such cells upon IRF4 loss. While we identify apoptosis as a critical pathway for the death of plasma cells caused by IRF4 loss, we also determine that IRF4 did not regulate the intrinsic apoptotic pathway directly. By using an inducible IRF4 deletion system in the presence of the overexpression of anti-apoptotic BCL2, we identify genes whose expression is coordinated by IRF4 and that in turn specify plasma cell identity and mitochondrial homeostas..

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Grants

Awarded by National Health and Medical Research Council (NHMRC, Australia)


Funding Acknowledgements

We acknowledge the help of the Walter and Eliza Hall Institute and AMREP Flow Cytometry Core Facilities and animal care facilities. This work was supported by the National Health and Medical Research Council (NHMRC, Australia) through program grant 1054925 and fellowships to A.S., A.K., S.L.N., and D.T. M.S.Y.L. was supported by a CRB Blackburn scholarship jointly from the NHMRC and the Royal Australasian College of Physicians; P.L.F. was supported by a Leukaemia Foundation of Australia Clinical Scholarship and a Royal College of Pathologists of Australasia Foundation Postgraduate Research Fellowship; S.N.W. was supported by the Walter and Eliza Hall Trust Centenary Fellowship; and W.S. was supported by a Walter and Eliza Hall Trust Centenary Fellowship sponsored by Commonwealth Serum Laboratories Limited.