Journal article
Polycomb repressive complex 2 is a critical mediator of allergic inflammation
CR Keenan, N Iannarella, AL Garnham, AC Brown, RY Kim, JC Horvat, PM Hansbro, SL Nutt, RS Allan
Jci Insight | AMER SOC CLINICAL INVESTIGATION INC | Published : 2019
Open access
Abstract
Strategies that intervene with the development of immune-mediated diseases are urgently needed, as current treatments mostly focus on alleviating symptoms rather than reversing the disease. Targeting enzymes involved in epigenetic modifcations to chromatin represents an alternative strategy that has the potential to perturb the function of the lymphocytes that drive the immune response. Here, we report that 2 major epigenetic silencing pathways are increased after T cell activation. By specifc inactivation of these molecules in the T cell compartment in vivo, we demonstrate that the polycomb repressive complex 2 (PRC2) is essential for the generation of allergic responses. Furthermore, we sh..
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Awarded by National Health and Medical Research Council of Australia
Awarded by Australian Research Council
Funding Acknowledgements
We thank Florence Cammas (IRCM, France) for the Cbx1, Cbx3, and Trim28<SUP>fl/fl</SUP> mice, Alexander Tarakhovsky (Rockefeller University) for the Ezh2<SUP>fl/fl</SUP> mice, and Stuart Orkin (Dana-Farber Cancer Institute, Harvard) for the Eed<SUP>fl/fl</SUP> mice. We also thank James Moon (Massachusetts General Hospital) for providing class II OVA-MHC tetramers (OVA-2C, OVA-3C). Assessment of total and OVA-specific IgE was generously performed by Kristy O'Donnell in the laboratory of David Tarlinton (Monash University). This work was supported by grants and fellowships from the National Health and Medical Research Council of Australia (1125436 to CRK, 1100451 to RSA, and 1058238 and 1054925 to SLN), the Australian Research Council (130100541 to RSA), and an American Asthma Foundation Grant (to SLN and RSA). This study was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme and the Australian Cancer Research Fund.