Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation

G Garg; A Muschaweckh; H Moreno; A Vasanthakumar; S Floess; G Lepennetier; R Oellinger; Y Zhan; T Regen; M Hiltensperger; C Peter; L Aly; B Knier; LR Palam; R Kapur; MH Kaplan; A Waisman; R Rad; G Schotta; J Huehn; A Kallies; T Korn

Journal article

Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation

G Garg, A Muschaweckh, H Moreno, A Vasanthakumar, S Floess, G Lepennetier, R Oellinger, Y Zhan, T Regen, M Hiltensperger, C Peter, L Aly, B Knier, LR Palam, R Kapur, MH Kaplan, A Waisman, R Rad, G Schotta, J Huehn Show all

Cell Reports | CELL PRESS | Published : 2019

DOI: 10.1016/j.celrep.2019.01.070

Abstract

An inflammatory environment threatens the stability of Foxp3 + Treg cells. Garg et al. show that by expressing the transcriptional regulator Blimp1, Treg cells resist the IL-6-driven loss of Foxp3 in inflamed tissues. Blimp1 prevents the methylation and reduced expression of Foxp3 through inhibition of the methyltransferase Dnmt3a.

University of Melbourne Researchers

Ajith Vasanthakumar Author

Axel Kallies Author

Related Projects (1)

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Awarded by Bundesministerium für Bildung und Forschung

Funding Acknowledgements

We would like to thank Veronika Husterer for her skillful technical assistance. We thank Beate Pietzsch for performing bisulfite pyrosequencing. We would also like to thank Veronika Holecska and Max Lohning (DRFZ Berlin) for providing us the isolated bones of Stat4<SUP>-/-</SUP> mice. We are grateful to Mohammad Oukka (University of Washington, Seattle, USA), Veit Buchholz (Technical University of Munich), and Stephan Kemmner (Technical University of Munich) for providing mouse strains. This work was supported by the Deutsche Forschungsgemeinschaft (SFB1054-B06 to T.K., TRR128 to T.K. and A.W., SyNergy to T.K., SFB738-C07 to J.H., SFB1243-A03 to G.S., and SFB1321-project number 329628492 to G.S.), the German Ministry of Education and Research (BMBF, T-B in NMO), the Helmholtz Gemeinschaft (Zukunftsthema "Immunology and Inflammation,'' ZT-0027 to J.H.), the ERC (CoG 647215 to T.K.), project grants from the National Health and Medical Research Council (1069075 and 1106378 to A.K.), a fellowship from the Sylvia and Charles Viertel foundation (to A.K.), and the National Multiple Sclerosis Society (NMSS RG 1707-28780 to A.W.). This study was also supported through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme.