CMMC: Eming, Sabine

Introduction

Recent advances in immunometabolism uncovered metabolic pathways in myeloid cells as one promising approach to regulate immune cell function. The role of metabolic pathways controlling immune cell function in tissue regenerative responses is unknown. The Eming group is interested to understand cellular mechanisms of metabolic control within the injured tissue and how this metabolic communication network can be exploited for the treatment of pathological wound healing conditions in patients.

Myeloid cells are an essential component of the body’s innate ability to restore tissue function after injury

Skin injury induces a highly dynamic cellular programme proceeding in sequential phases of antimicrobial defence, followed by tissue growth and differentiation. Cells of the myeloid cell lineage are an essential component of the body’s innate ability to restore tissue function after injury. Our previous work showed that to ensure optimal skin wound healing, macrophages need to initially adopt a pro-inflammatory and pro-angiogenic phenotype (characterized by a type-1 immune response), and later once immediate danger has passed to acquire a resolution phenotype (characterized by a type-2 immune response) to promote repair. Our aim is to further explore signalling pathways and transcriptional networks in macrophages that coordinate their functional plasticity during the sequential repair stages and to understand whether metabolic programmes impact these processes.

Perspectives

Our studies may inspire novel and exciting avenues to understand perturbed immune cell function and to develop therapeutic approaches for the treatment of chronic inflammation and pathological wound healing conditions in patients.

Project Related Publications

Kiesewetter A, Cursiefen C, Eming SA*, Hos D*. (2019) Phase-specific functions of macrophages determine injury-mediated corneal hem- and lymphangiogenesis (* corresponding authors). Sci Rep 9:308.
Do, N.N., Willenborg, S., Eckes, B., Sengle, G., Zauke, F., Eming. S.A. (2018). Myeloid cell-restricted STAT3 signaling controls a cell autonomous anti-fibrotic repair program. J Immunol 201:663-674.
Eming, S.A., Wynn, T.M., and Martin, P. (2017). Inflammation and metabolism in tissue regeneration and repair. Science 356, 1026-1030.
Knipper, J.A., Willenborg, S., Brinckmann, J., Bloch, W., Maaß, T., Wagener, R., Willenborg, S., Krieg, T., Sutherland, T., Migge, T., Richardson, R., Hammerschmidt, M., Allen, J.E., and Eming, S.A. (2015). IL-4Rα signaling in myeloid cells controls collagen fibril assembly in skin repair. Immunity 43, 803-816.
Ding, X., Lucas, T., Marcuzzi, G.P., Pfister, H., and Eming, S.A. (2015). Distinct functions of epidermis- and myeloid cell specific VEGF-A in human papillomavirus type 8-mediated tumorigenesis. Cancer Res. 75, 330-343.
Knuever, J., Willenborg, S., Ding, X., Akyüz, M.D., Partridge, L., Niessen, C.M., Brüning, J.C., and Eming, S.A. (2015). Myeloid cell-restricted Insulin/IGF-1 receptor deficiency protects against skin inflammation. J. Immunol. 195, 5296-5308.
Eming, S.A., Martin, P., and Tomic-Canic, M. (2014). Wound Repair and Regeneration: Mechanisms, signaling, and translation. Sci. Transl. Med. 6, 265sr6.
Willenborg, S., Lucas, T., Geert van Loo, G., Knipper, J., Krieg, T., Haase., I., Brachvogel, B., Hammerschmidt, M., Nagy, A., Ferrara, N., Pasparakis, M., and Eming, S.A. (2012) CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair. Blood 120, 613-625.
Lucas T, Waisman A, Ranjan R, Roes J, Krieg T, Müller W, Roers A, Eming SA, (2010) Differential roles of macrophages in diverse phases of skin repair. J Immunol 184(7):3964-77