The role of RANK/RANKL signaling for skin homeostasis and barrier function during anti-microbial immune responses

    Staphylococcus aureus (S. aureus) is a leading cause of skin and soft tissue infection. We have shown that during cutaneous S. aureus infection signaling through the receptor activator of NF‑kB (RANK) and its ligand RANKL controls the induction of immunosuppressive cells like Treg and eosinophilic MDSC resulting in an increased skin lesion size and an impaired epithelial barrier integrity. Now we will analyze the cellular and molecular mechanisms underlying RANK/RANKL-induced immunosuppression and investigate whether this signaling pathway might affect barrier integrity in different organs or in response to different external factors.

    Research area: Skin immunology

    Prof. Dr. rer. nat. Karin Loser

    Funding period: July 2012 - June 2024 (since July 2021 ath Carl von Ossietzky University in Oldenburg)

    • Publications

      Original articles

      • Christmann C, Zenker S, Martens L, Hübner J, Loser K, Vogl T,Roth J (2021) Interleukin 17 promotes expression of alarmins S100A8 and S100A9 during the inflammatory response of keratinocytes. Front Immun 11: 599947

      • Ostkamp P, Salmen A, Pignolet B, Görlich D, Andlauer TFM, Schulte-Mecklenbeck A, Gonzalez-Escamilla G, Bucciarelli F, Gennero I, Breuer J, Antony G, Schneider-Hohendorf T, Mykicki N, Bayas A, Then Bergh F, Bittner S, Hartung HP, Friese MA, Linker RA, Luessi F, Lehmann-Horn K, Mühlau M, Paul F, Stangel M, Tackenberg B, Tumani H, Warnke C, Weber F, Wildemann B, Zettl UK, Ziemann U, Müller-Myhsok B, Kümpfel T, Klotz L, Meuth SG, Zipp F, Hemmer B, Hohlfeld R, Brassat D, Gold R, Gross CC, Lukas C, Groppa S, Loser K, Wiendl H, Schwab N (2021) Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity. German Competence Network Multiple Sclerosis (KKNMS) and the BIONAT Network. Proc Natl Acad Sci U S A 5 118(1):e2018457118

      • Martin B, Schepmann D, Bernal FA, Schmidt TJ, Che T, Loser K, Wünsch B (2020) Enantiomerically Pure Quinoline-Based κ-Opioid Receptor Agonists: Chemoenzymatic Synthesis and Pharmacological Evaluation. ChemMedChem 5;15(15):1408-1420

      • Weishaupt C, Steinert M, Brunner G, Schulze HJ, Fuhlbrigge RC, Goerge T, Loser K. Activation of human vascular endothelium in melanoma metastases induces ICAM-1 and E-selectin expression and results in increased infiltration with effector lymphocytes. Exp Dermatol. 2019 Aug 24. doi: 10.1111/exd.14023. [Epub ahead of print]
      • Klotz L, Eschborn M, Lindner M, Liebmann M, Herold M, Janoschka C, Torres Garrido B, Schulte-Mecklenbeck A, Gross CC, Breuer J, Hundehege P, Posevitz V, Pignolet B, Nebel G, Glander S, Freise N, Austermann J, Wirth T, Campbell GR, Schneider-Hohendorf T, Eveslage M, Brassat D, Schwab N, Loser K, Roth J, Busch KB, Stoll M, Mahad DJ, Meuth SG, Turner T, Bar-Or A, Wiendl H. Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects. Sci Transl Med. 2019 May 1;11(490). pii: eaao5563.
      • Tangherlini G, Kalinin DV, Schepmann D, Che T, Mykicki N, Ständer S, Loser K, Wünsch B. Development of novel quinoxaline-based kappa-opioid receptor (KOR) agonists for the treatment of neuroinflammation. J Med Chem.2019 Jan 24;62(2):893-907.
      • Breuer J, Loser K, Mykicki N, Wiendl H, Schwab N. Does the environment influence multiple sclerosis pathogenesis via UVB light and/or induction of vitamin D? J Neuroimmunol. 2018 May 18. pii: S0165-5728(17)30478-2. doi: 10.1016/j.jneuroim.2018.05.006. [Epub ahead of print]
      • Vogl T, Stratis A, Wixler V, Völler T, Thurainayagam S, Jorch SK, Zenker S, Dreiling A, Chakraborty D, Fröhling M, Paruzel P, Wehmeyer C, Hermann S, Papantonopoulou O, Geyer C, Loser K, Schäfers M, Ludwig S, Stoll M, Leanderson T, Schultze JL, König S, Pap T, Roth J. Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation. J Clin Invest. 2018 May 1;128(5):1852-1866. doi: 10.1172/JCI89867.
      • Mykicki, N., Klenner, L., Baumann, C., Auriemma, M., Sternemann, C., Soeberdt, M., Elliott, G. R., Abels, C., Luger, T. A. and Loser, K. (2017) The tripeptide KdPT ameliorates ongoing psoriasis-like skin inflammation in murine and human skin. Exp Dermatol, 26: 328–334. (doi:10.1111/exd.13145)
      • Mykicki N, Herrmann AM, Schwab N, Deenen R, Sparwasser T, Limmer A, Wachsmuth L, Klotz L, Köhrer K, Faber C, Wiendl H, Luger TA, Meuth SG, Loser K. Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease. Sci Transl Med. 2016 Oct 26;8(362):362ra146.
      • Leite Dantas R, Masemann D, Schied T, Bergmeier V, Vogl T, Loser K, Brachvogel B, Varga G, Ludwig S, Wixler V. Macrophage-mediated psoriasis can be suppressed by regulatory T lymphocytes. J Pathol. 2016 Nov;240(3):366-377. doi: 10.1002/path.4786.
      • Wegner J, Loser K, Apsite G, Nischt R, Eckes B, Krieg T, Werner S, Sorokin L. Laminin ?5 in the keratino-cyte basement membrane is required for epidermal-dermal intercommunication. Matrix Biol. 2016 Dec;56:24-41. doi: 10.1016/j.matbio.2016.05.001.
      • Herold M, Posevitz V, Chudyka D, Hucke S, Groß C, Kurth F, Leder C, Loser K, Kurts C, Knolle P, Klotz L, Wiendl H (2015) B7-H1 selectively controls TH17 differentiation and central nervous system autoimmunity via a novel Non-PD-1-mediated pathway. J Immunol 195: 3584-3595.
      • Klenner L, Hafezi W, Clausen BE, Lorentzen EU, Luger TA, Beissert S, Kühn JE, Loser K (2015) Cutaneous RANK-RANKL signaling upregulates CD8-mediated antiviral immunity during Herpes simplex virus infection by preventing virus-induced Langerhans Cell apoptosis. J Invest Dermatol 135: 2676-2687.
      • Breuer J*, Schwab N*, Schneider-Hohendorf T, Marziniak M, Mohan H, Bhatia U, Gross CC,Clausen BE, Weishaupt C, Luger TA, Meuth SG, Loser K*, Wiendl H* (2014) Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity. Ann Neurol 75: 739-758. *equal contribution.
      • Petersen B, Wolf M, Austermann J, van Lent P, Foell D, Ahlmann M, Kupas V, Loser K, Sorg C, Roth J, Vogl T (2013) The alarmin Mrp8/14 as regulator of the adaptive immune response during allergic contact dermatitis. EMBO J 32: 100-111.