The groups of Matthias Lochner and Stefan Flöß work together to study the impact of specific epigenetic modifications on the biology of innate lymphoid cell (ILC)-populations under homeostatic and inflammatory conditions. Epigenetic modifications such as DNA methylation play an essential role for imprinting specific transcriptional patterns in immune cells. In CD4+ T helper (Th) cells for example, specific demethylated DNA regions have been identified that are critical for the identity, function and lineage stability of the different Th subsets. Considering the striking similarities between Th cell lineages and innate lymphoid cell (ILC) populations regarding the dependency on specific transcription factors and expression of signature cytokines, it is likely that also ILC populations can be functionally characterized by differentially methylated regions in their genomic DNA. State-of-the art techniques such as genome-wide sequencing allow us to establish the methylomes of ILC subtypes and to define unique epigenetic signatures in ILC subpopulations. Such signatures represent not only valuable tools to study ILCs under homeostatic as well as under inflammatory conditions in vivo, but can also be used to better understand the transcriptional regulation of ILC-related genes. The basic in vitro and in vivo research that is carried out in the murine system will be complemented by approaches that aim to define specific epigenetic signatures in human ILC populations and to study their functional significance. Together, the identification and characterization of specific epigenetic signatures in ILCs will be an important step for the discovery of key pathways and molecular mechanisms in ILC differentiation and function.
- Friedrich, C., P. Mamareli, S. Thiemann, F. Kruse, Z. Wang, B. Holzmann, T. Strowig, T. Sparwasser and Lochner, MyD88 Signaling in Dendritic Cells and the Intestinal Epithelium Controls Immunity against Intestinal Infection with C. rodentium. PloS Path, 2017. 13:5.
- Yang, B.H., S. Hagemann, P. Mamareli, U. Lauer, U. Hoffmann, M. Beckstette, L. Fohse, I. Prinz, J. Pezoldt, S. Suerbaum, T. Sparwasser, A. Hamann, Floess, J. Huehn, and M. Lochner, Foxp3 T cells expressing RORgammat represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunol, 2016. 9:444-457.
- Yang, B.H.*, Floess*, S. Hagemann, I.V. Deyneko, L. Groebe, J. Pezoldt, T. Sparwasser, M. Lochner, and J. Huehn, Development of a unique epigenetic signature during in vivo Th17 differentiation. Nucleic Acids Res, 2015. 43(3): 1537-48. (*contributed equally)
- Schreiber, L., B. Pietzsch, Floess, C. Farah, L. Jansch, I. Schmitz, and J. Huehn, The Treg-specific demethylated region stabilizes Foxp3 expression independently of NF-kappaB signaling. PLoS One, 2014. 9(2): e88318.
- Berod, L., C. Friedrich, A. Nandan, J. Freitag, S. Hagemann, K. Harmrolfs, A. Sandouk, C. Hesse, C.N. Castro, H. Bahre, S.K. Tschirner, N. Gorinski, M. Gohmert, C.T. Mayer, J. Huehn, E. Ponimaskin, W.R. Abraham, R. Muller, Lochner*, and T. Sparwasser*, De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med, 2014. 20(11): 1327-33. (*contributed equally)
- Toker, A., D. Engelbert, G. Garg, J.K. Polansky, Floess, T. Miyao, U. Baron, S. Duber, R. Geffers, P. Giehr, S. Schallenberg, K. Kretschmer, S. Olek, J. Walter, S. Weiss, S. Hori, A. Hamann, and J. Huehn, Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus. J Immunol, 2013. 190(7): 3180-8.
- Steinfelder, S., Floess, D. Engelbert, B. Haeringer, U. Baron, L. Rivino, B. Steckel, A. Gruetzkau, S. Olek, J. Geginat, J. Huehn, and A. Hamann, Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells. Blood, 2011. 117(10): 2839-46.
- Sawa, S., Lochner, N. Satoh-Takayama, S. Dulauroy, M. Berard, M. Kleinschek, D. Cua, J.P. Di Santo, and G. Eberl, RORgammat+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat Immunol, 2011. 12(4): 320-6.
- Lochner, M., C. Ohnmacht, L. Presley, P. Bruhns, M. Si-Tahar, S. Sawa, and G. Eberl, Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORgamma t and LTi cells. J Exp Med, 208(1): 125-34.
- Sawa, S., M. Cherrier, Lochner, N. Satoh-Takayama, H.J. Fehling, F. Langa, J.P. Di Santo, and G. Eberl, Lineage relationship analysis of RORgammat+ innate lymphoid cells. Science, 2010. 330(6004): 665-9.
- Floess, S., J. Freyer, C. Siewert, U. Baron, S. Olek, J. Polansky, K. Schlawe, H.D. Chang, T. Bopp, E. Schmitt, S. Klein-Hessling, E. Serfling, A. Hamann, and J. Huehn, Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol, 5(2): e38.