We are investigating immune cell populations in the context of healthy tissue biology and following pathologic changes of tissues and organs. In our previous work, we have identified a population of regulatory T cells which can promote tissue homeostasis and regeneration (Delacher M et al., Nat Immunol 2017). We could further describe the two-step differentiation process of this special subset of regulatory T cells from progenitors residing in the lymphoid tissue (Delacher M et al., Immunity 2020), as well as the system-immunological consequences of interfering with this differentiation process (Delacher M et al., Nat Comm 2019). In translational studies, we were able to identify the hitherto unknown regulatory T cell subset in human which is involved in tissue regeneration (Delacher M et al., Immunity 2021).
In parallel, we are investigating other immune cell populations for their tissue regenerative potential. Here, we especially focus on the concept that tumors might exploit this tissue regenerative program present in immune cells. Our research might shed a new light on tissue immunology in the context of healthy and diseased tissues, investigating this novel concept in the settings of cancer, chronic and acute infections. In summary, our laboratory is interested in the following questions:
1) How do tissues regenerate? And how does the immune system support tissue homeostasis and regeneration?
2) How does tissue regeneration work upon acute infection, radiation injuries or various types of tissue damage? What is the contribution of the different effector cells of the immune system?
3) What is the function of tissue-regenerative immune cells in the context of tissue ageing, chronic inflammation or neoplastic diseases? Do they support the immunoevasion of tumors?
4) How can we translate our research into the clinic in order to improve patient care?
In the Delacher Lab, we are using a wide variety of experimental and bioinformatic methods. For this, we are working together with collaboration partners from the Institute, the University Medical Center, as well as other researchers in and outside of Germany. The figure below shows a typical workflow in our lab:
1) We receive fresh tissue from surgical procedures performed at the University Medical Center in Mainz or other Medical Centers in the area
2) In collaboration with the department of pathology, healthy and neoplastic tissue are identified and anatomically separated
3) Tissues are digested in a mixture of enzymes in order to isolate single cells from the tissue
4) The single-cell suspension can now be further separated into subsets
5) Via physical separation methods such as gradient centrifugation or filtration, immune cell subsets can be separated from each other
6) We then use magnetic separation methods to retain target cells using a strong magnetic field, while non-target cells can be washed off
7) Target cells can be eluted and analyzed, e.g. using flow cytometry or microscopy
8) To analyze target cells on a molecular level, they are sorted according to their surface characteristics with a fluorescence activated cell sorting machine. The now extremely pure cell population can be used for detailed downstream analyses, e.g.
Braband, K.L., Kaufmann, T., Floess, S., Zou, M., Huehn, J., Delacher, M.: Stepwise acquisition of unique epigenetic signatures during differentiation of tissue Treg cells. Front Immunol 2022: https://pubmed.ncbi.nlm.nih.gov/36569861/
Delacher, M., Simon, M., Sanderink, L., Hotz-Wagenblatt, A., Wuttke, M., Schambeck, K., Schmidleithner, L., Bittner, S., Pant, A., Ritter, W., Hehlgans, T., Riegel, D., Schneider, V., Groeber-Becker, F., Eigenberger, A., Gebhardt, C., Strieder, N., Fischer, A., Rehli, M., Hoffmann, P., Edinger, M., Strowig, T., Huehn, J., Schmidl, C., Prantl, L., Werner, J., Brors, B., Imbusch, C.D., Feuerer, M: Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells. Immunity 2021: https://pubmed.ncbi.nlm.nih.gov/33789089/
Delacher, M., Barra, M. M., Herzig, Y., Eichelbaum, K., Mahmoud-Reza, R., Richards, DM., Träger, U., Hofer, AC., Kazakov, A., Braband, KL., Gonzalez, M., Wöhrl, L., Schambeck, K., Imbusch, C. D., Abramson, J., Krijgsveld, J., Feuerer, M: Quantitative proteomics identifies TCF1 as a negative regulator of Foxp3 expression in conventional T cells. iScience 2020: https://pubmed.ncbi.nlm.nih.gov/32422593/
Delacher, M., Imbusch, C. D., Hotz-Wagenblatt, A., Mallm, J. P., Bauer, K., Simon, M., Riegel, D., Rendeiro, A. F., Bittner, S., Sanderink, L., Pant, A., Schmidleithner, L., Braband, K. L., Echtenachter, B., Fischer, A., Giunchiglia, V., Hoffmann, P., Edinger, M., Bock, C., Rehli, M., Brors, B., Schmidl, C., Feuerer, M: Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF. Immunity 2020: https://pubmed.ncbi.nlm.nih.gov/31924477/
Delacher, M., Schmidl, C., Herzig, Y., Breloer, M., Hartmann, W., Brunk, F., Kagebein, D., Trager, U., Hofer, A. C., Bittner, S., Weichenhan, D., Imbusch, C. D., Hotz-Wagenblatt, A., Hielscher, T., Breiling, A., Federico, G., Grone, H. J., Schmid, R. M., Rehli, M., Abramson, J., Feuerer, M: Rbpj expression in regulatory T cells is critical for restraining TH2 responses. Nature Communication 2019: https://pubmed.ncbi.nlm.nih.gov/30962454/
Delacher, M., Imbusch, C. D., Weichenhan, D., Breiling, A., Hotz-Wagenblatt, A., Trager, U., Hofer, A. C., Kagebein, D., Wang, Q., Frauhammer, F., Mallm, J. P., Bauer, K., Herrmann, C., Lang, P. A., Brors, B., Plass, C., Feuerer, M: Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues. Nature Immunology 2017: https://pubmed.ncbi.nlm.nih.gov/28783152/
Event:European Single Cell Discovery Symposium 2022
Location: Frankfurt
Date: 2. Juni 2022
Title: Using single cell genomics to understand tissue immunology
Link Presentation
Event: Virtual MACS Genomics Day 2021
Location: virtuell
Date: 23. September 2021
Title: Using single cell genomics to understand tissue immunology
Link Presentation
Univ.-Prof. Dr. Michael Delacher
delacher@uni-mainz.de
Tel: +49 (0)6131 17-6574
Deutsch
