1.) We established two mouse models that focus on essential immune response genes. The first is a CD83-reporter mouse model which allows us to carry out in vivo monitoring of CD83, the best known surface marker for DC activation. Although the ligand for CD83 is still unknown, CD83 itself plays an important role for the intracellular interactions of DCs, T cells and B cells. The upregulation of CD83 during the activation of these important immune cell, makes CD83 a fascinating target for our studies. We examine CD83 expression on host and donor DCs, T and B cells in skin transplantation and experimental autoimmune encephalomyelitis (EAE) models.
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Dr. rer. nat. Matthias Lechmann, PhD
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Research Interests:
Immunobiology of Dendritic cells and T-cells. We are interested in the regulatory mechanisms balancing Th1/Th2 immune responses and the development of regulatory T cells in vivo.
2.) The second model focuses on functional studies of thymic stromal lymphopoietin (TSLP), thought to be the “missing link” between DC activation and allergic responses. To further characterize the role of TSLP in vivo, we generated a TSLP KO mouse. Using this KO mouse we will further characterize the function of TSLP in different inflammatory disease, infections as well as in models for autoimmunity.
3.) We developed a fast and highly specific aptamer-based screening technology for the detection of biomarkers on living cells. In contrast to conventional methods, our new aptamer-based technique discovers biomarkers in their native states and conformation. In addition to facilitating biomarker identification, such aptamers can be directly used for a number of other applications, including isolation and visualization of cell as well as cell tracking in vivo. Using this technique we want to select aptamers specific for T cell epitopes of known tumor antigens and furthermore identify new tumor targets to improve tumor-specific DC-vaccines.
Team:
Hr. Dipl. biol. Simon Kreiser, Doktorand
Fr. Dipl. hum. biol. Jenny Eckhardt
Astrid Mainka, MTA
Selected References:
Magalhaes JG, Rubino SJ, Travassos LH, Le Bourhis L, Duan W, Sellge G, Geddes K, Reardon C, Lechmann M, Carneiro LA, Selvanantham T, Fritz JH, Taylor BC, Artis D, Mak TW, Comeau MR, Croft M, Girardin SE, Philpott DJ. Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal activation. Proc Natl Acad Sci U S A. 2011 Aug 19. [Epub ahead of print]
Reardon C, Lechmann M, Brüstle A, Gareau MG, Shuman N, Philpott D, Ziegler SF, Mak TW. Thymic Stromal Lymphopoetin-Induced Expression of the Endogenous Inhibitory Enzyme SLPI Mediates Recovery from Colonic Inflammation. Immunity. 2011 Aug 26;35(2):223-35. Epub 2011 Aug 4.
Lechmann M, Shuman N, Wakeham A, Mak TW. The CD83 reporter mouse elucidates the activity of the CD83 promoter in B, T, and dendritic cell populations in vivo. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11887-92.
Berezovski, M. V., Lechmann, M., Musheev, M. U., Mak, T. W., and Krylov, S. N. (2008). Aptamer-facilitated biomarker discovery (AptaBiD). Journal of the American Chemical Society 130, 9137-9143.
Kummer, M., Turza, N. M., Muhl-Zurbes, P., Lechmann, M., Boutell, C., Coffin, R. S., Everett, R. D., Steinkasserer, A., and Prechtel, A. T. (2008). Herpes simplex virus type 1 induces CD83 degradation in mature dendritic cells with immediate-early kinetics via the cellular proteasome. Experimental Dermatology 17, 256.
Kummer, M., Turza, N. M., Muhl-Zurbes, P., Lechmann, M., Boutell, C., Coffin, R. S., Everett, R. D., Steinkasserer, A., and Prechtel, A. T. (2007). Herpes simplex virus type 1 induces CD83 degradation in mature dendritic cells with immediate-early kinetics via the cellular proteasome. Journal of Virology 81, 6326-6338.
Zinser E, Lechmann M, Golka A, Hock B and Steinkasserer A. Determination of the inhibitory activity and biological half-live of soluble CD83: comparison of wild type and mutant isoforms.
Immunobiol. 211(6-8): 449-53 (2006)
Lechmann M, Kotzor N, Zinser E, Prechtel A and Steinkasserer A. CD83 is a Dimer. Comparative Analysis of Monomeric and Dimeric Isoforms.
Biochem. Biophys. Res. Commun. 329(1):132-139 (2005)
Zinser E, Lechmann M, Golka A, Lutz MB and Steinkasserer A. Prevention and Treatment of Experimental Autoimmune Encephalomyelitis (EAE) by Soluble CD83.
J. Exp. Med. 200: 345-351 (2004)
Kotzor N, Lechmann M, Zinser E and Steinkasserer A. The soluble form of CD83 dramatically changes the cytoskeleton of dendritic cells.
Immunobiol. 209: 129-140 (2004)
Kobelt D, Lechmann M and Steinkasserer A. The interaction between Dendritic cells and Herpes simplex virus-1.
Curr. Topics. Microbiol. Immunol. 276: 145-161 (2003)
Lechmann M, Zinser E, Golka A and Steinkasserer A. The role of CD83 in the immunomodulation of dendritic cells.
Int.l Arch. Allergy Immunol. 129: 113-118 (2002)
Lechmann M, Berchtold S, Hauber J and Steinkasserer A. CD83 on dendritic cells: more than just a marker for maturation.
TRENDS in Immunol. 23: 273-275 (2002)
Lechmann M, Kremmer E, Sticht H and Steinkasserer A. Overexpression, purification, and biochemical characterization of the extracellular human CD83 domain and generation of monoclonal antibodies.
Prot. Exp. Purif. 24: 445-452 (2002)
Lechmann M, Krooshoop DJEB, Dudziak D, Kremmer E, Kuhnt C, Figdor CG, Schuler G and Steinkasserer A. The extracellular domain of CD83 inhibits dendritic cell-mediated T cell stimulation and binds to a ligand on dendritic cells.
J. Exp. Med. 194: 1813-1321 (2001)
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