Center for Molecular Medicine Cologne

Eming, Sabine - C 06

Metabolic regulation of myeloid cells in tissue repair and regeneration

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.

  1. 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.
  2. 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.
  3. Eming, S.A., Wynn, T.M., and Martin, P. (2017). Inflammation and metabolism in tissue regeneration and repair. Science 356, 1026-1030.
  4. 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.
  5. 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.
  6. 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.
  7. Eming, S.A., Martin, P., and Tomic-Canic, M. (2014). Wound Repair and Regeneration: Mechanisms, signaling, and translation. Sci. Transl. Med. 6, 265sr6.
  8. 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.
  9. 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
  • Welcker D, Stein C, Feitosa NM, Armistead J, Zhang JL, Lutke S, Kleinridders A, Bruning JC, Eming SA, Sengle G, Niehoff A, Bloch W, and Hammerschmidt M (2021). Hemicentin-1 is an essential extracellular matrix component of the dermal-epidermal and myotendinous junctions. Sci Rep11, 17926. doi:10.1038/s41598-021-96824-4.
    • Willenborg S, Sanin DE, Jais A, Ding X, Ulas T, Nuchel J, Popovic M, MacVicar T, Langer T, Schultze JL, Gerbaulet A, Roers A, Pearce EJ, Bruning JC, Trifunovic A, and Eming SA (2021). Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing. Cell Metab33, 2398-2414 e2399. doi:10.1016/j.cmet.2021.10.004.
    • Ding X, Kakanj P, Leptin M, and Eming SA (2021). Regulation of the Wound Healing Response during Aging. J Invest Dermatol141, 1063-1070. doi:10.1016/j.jid.2020.11.014.
    • Eming SA, Murray PJ, and Pearce EJ (2021). Metabolic orchestration of the wound healing response. Cell Metab33, 1726-1743. doi:10.1016/j.cmet.2021.07.017.
    • Hadrian K, Willenborg S, Bock F, Cursiefen C, Eming SA, and Hos D (2021). Macrophage-Mediated Tissue Vascularization: Similarities and Differences Between Cornea and Skin. Front Immunol12, 667830. doi:10.3389/fimmu.2021.667830.
    • Ding X, Willenborg S, Bloch W, Wickstrom SA, Wagle P, Brodesser S, Roers A, Jais A, Bruning JC, Hall MN, Ruegg MA, and Eming SA (2020). Epidermal mammalian target of rapamycin complex 2 controls lipid synthesis and filaggrin processing in epidermal barrier formation. J Allergy Clin Immunol145, 283-300 e288. doi:10.1016/j.jaci.2019.07.033.
                                                                              • Kakanj P, Eming SA, Partridge L, and Leptin M (2020). Long-term in vivo imaging of Drosophila larvae. Nat Protoc15, 1158-1187. doi:10.1038/s41596-019-0282-z.
                                                                                              • Kim CS, Ding XL, Allmeroth K, Biggs LC, Kolenc OI, L'Hoest N, Chacon-Martinez CA, Edlich-Muth C, Giavalisco P, Quinn KP, Denzel MS, Eming SA, and Wickstrom SA (2020). Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle. Cell Metabolism32, 629-+. doi:10.1016/j.cmet.2020.08.011.
                                                                                                                                                                                                                                                                    • Schiffmann LM, Werthenbach JP, Heintges-Kleinhofer F, Seeger JM, Fritsch M, Gunther SD, Willenborg S, Brodesser S, Lucas C, Jungst C, Albert MC, Schorn F, Witt A, Moraes CT, Bruns CJ, Pasparakis M, Kronke M, Eming SA, Coutelle O, and Kashkar H (2020). Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth. Nature Communications11. doi:Artn 3653 10.1038/S41467-020-17472-2.
                                                                                                                                                                                                                                                                    • Schönborn K, Willenborg S,  Schulz J N, Imhof T, Eming S A, Quondamatteo F, Brinckmann J,  Niehoff A, Paulsson M, Koch M, Eckes B, Krieg T. Role of collagen XII in skin homeostasis and repair. Matrix Biol 2020 Vol. 94 Pages 57-76, Accession Number: 32890632 DOI: 10.1016/j.matbio.2020.08.002.
                                                                                                                                                                                                                                                                    Prof. Dr. Sabine Eming CMMC Cologne
                                                                                                                                                                                                                                                                    Prof. Dr. Sabine Eming

                                                                                                                                                                                                                                                                    Clinic and Polyclinic of Dermatology and Venereology

                                                                                                                                                                                                                                                                    CMMC - Vice Chair

                                                                                                                                                                                                                                                                    CMMC - PI - C 06

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                                                                                                                                                                                                                                                                    Clinic and Polyclinic of Dermatology and Venereology

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                                                                                                                                                                                                                                                                    Publications - Sabine Eming

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