Work Group PD Dr. Matthias Lochner
In the research group of Mucosal Infection Immunology we investigate several key aspects of mucosal infection biology. This includes a better understanding of host-pathogen interactions at the mucosal barrier site and in particular the mechanisms that activate and regulate the infection-induced immune response. In addition, we explore the (epi) genetic background as well as the molecular and metabolic processes of infection-associated immune responses. Most importantly, we search for novel therapeutic targets to modulate the immune response aiming to translate the findings of our basic research into clinical applications.
Targeting the intracellular metabolism of immune cells is a promising novel strategy for immunomodulation. Our previous work suggested that intracellular de novo fatty acid synthesis represents an important metabolic checkpoint for the reciprocal differentiation of Th17 versus regulatory T cells. One focus of our work is to understand the impact of central metabolic processes on intestinal immune responses under in vivo conditions. We use established as well as newly generated genetic mouse models that allow for the deletion of the key metabolic enzymes in specific immune- and non-immune cells such as T-cells, innate lymphoid cells (ILC) and intestinal epithelial cells. We also assess the potential of pharmacologic modulation of metabolic pathways and translate these findings into the human system.
It has been a long-standing focus of our research group to analyze the immune response in mucosal inflammation and infection with specific bacterial pathogens. Currently, we are using mouse models to investigate basic principles of the immune response against pathogens such as C. rodentium or C. difficile in the intestine as well as S. pneumoniae in the lung. Another focus of our lab is on the identification and functional characterization of epigenetic signature genes in T cells and ILC lineages, which will be an important step for the discovery of key pathways and molecular mechanisms in the differentiation and function of these cell types in intestinal infection and inflammation.
Our research is supported by grants of the German Research Foundation DFG (LO1415/7-1 and DFG Priority program 1937) and of Lower Saxony (R2N).
Most important publications:
- Mamareli P, F Kruse, C Friedrich, N Smit, T Strowig, T Sparwasser, M Lochner. 2019. Epithelium-specific MyD88 signaling, but not DCs or macrophages, control acute intestinal infection with Clostridium difficile. Eur J immunol. 49(5):747-757
- Raud B, DG Roy, AS Divakaruni, TN Tarasenko, R Franke, EH Ma, B Samborska, WY Hsieh, AH Wong, P Stüve, CA Schrauf, M Guderian, M Lochner, S Rampertaap, K Romito, J Monsale, M Brönstrup, SJ Bensinger, AN Murphy, PJ McGuire, RG Jones, T Sparwasser, L Berod. 2018. Etomoxir actions on regulatory and memory T cells are independent of Cpt1a-mediated fatty acid oxidation. Cell Metab. 28(3):504-515.
- Friedrich C, P Mamareli, S Thiemann, F Kruse, Z Wang, B Holzmann, T Strowig, T Sparwasser, M Lochner. 2017. MyD88 signaling in dendritic cells and the intestinal epithelium controls immunity against intestinal infection with C. rodentium. PloS Pathog. 13:5.
- Yang, BH, S Hagemann, P Mamareli, U Lauer, U Hoffmann, M Beckstette, L Fohse, I Prinz, J Pezoldt, S Suerbaum, T Sparwasser, A Hamann, S Floess, J Huehn, M Lochner. 2016. Foxp3(+) T cells expressing RORgammat represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunol. 9:444-457.
- Wang, Z, C Friedrich, SC Hagemann, WH Korte, N Goharani, S Cording, G Eberl, T Sparwasser, M Lochner. 2014. Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium. Mucosal Immunol. 7:1290-1301.
- Berod, L, C Friedrich, A Nandan, J Freitag, S Hagemann, K Harmrolfs, A Sandouk, C Hesse, CN Castro, H Bahre, SK Tschirner, N Gorinski, M Gohmert, CT Mayer, J Huehn, E Ponimaskin, WR Abraham, R Muller, M Lochner*, T Sparwasser*. 2014. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med 20:1327-1333. (*contributed equally)
- Sawa, S, M Lochner, N Satoh-Takayama, S Dulauroy, M Berard, M Kleinschek, D Cua, JP Di Santo, G Eberl. 2011. RORgammat+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat Immunol. 12:320-326.
- Lochner, M, C Ohnmacht, L Presley, P Bruhns, M Si-Tahar, S Sawa, G Eberl. 2011. Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORgamma t and LTi cells. J Exp Med. 208:125-134.
- Satoh-Takayama, N, CA Vosshenrich, S Lesjean-Pottier, S Sawa, M Lochner, F Rattis, JJ Mention, K Thiam, N Cerf-Bensussan, O Mandelboim, G Eberl, JP Di Santo. 2008. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29:958-970.
- Lochner, M, L Peduto, M Cherrier, S Sawa, F Langa, R Varona, D Riethmacher, M Si-Tahar, JP Di Santo, G Eberl. 2008a. In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgamma t+ T cells. J Exp Med. 205:1381-1393.