Involvement of skin-associated lymphoid tissue for therapeutic interventions of immunopathological disorders

Prof. Dr. Uwe Ritter

Address

Devision for Immunology

LIT Leibniz Institute for Immunotherapy
University of Regensburg
Franz-Josef-Strauß-Allee 11
93053 Regensburg

Phone: +49-(0)941-944-18125
Fax: +49-(0)941-944-38123
Email: uwe.ritter(at)ukr.de

Focus of research

The so-called skin-associated lymphatic tissue (SALT) represents the main focus of our work. We are investigating, how antigen-specific immune responses are induced and regulated in skin-draining lymph nodes. In this context we are focused on myeloid cells and adaptive immune responses, resulting from interactions between antigen-presenting cells and T cells.

We are characterizing the cellular checkpoints, resulting in the initiation and regulation of T cell mediated immunity. The impact of myeloid subsets in immune regulation and wound healing is of special interest.

Our goal is the identification of exo- and endogenous mediators that are interfering with checkpoints of immunoregulation. In this context we are aiming to modulate these immune checkpoints, in order to cure immunopathological manifestations such as autoimmune diseases.

The projects are and have been financed through third-party funds. Many thanks to:

  • Deutsche Forschungsgemeinschaft
    » compare
  • Bayerische Forschungsstiftung
  • Jung-Stiftung für Wissenschaft und Forschung
  • Bayerisches Staatsministerium für Wissenschaft und Kunst
    » Details

Research topics

Immunomodulation by microbial components

Our immune system is in permanent contact with the body's specific bacterial milieu. These so-called commensal bacteria are also important for the optimal barrier function of our healthy skin. Under certain circumstances, however, some of commensal bacteria can develop resistance to antibiotics and cause fulminant infections.

The aim of this research project is to understand why our immune system detects but tolerates commensal skin bacteria such as Staphylococcus epidermidis without inducing active defense mechanisms.  On the other hand, we intend to specifically overcome this immunotolerance in order to achieve protective immune responses against multi-resistant bacteria.

The specific modulation of these tolerance mediating triggers can also be included in the develop new targets against chronic autoimmune and tumor diseases. This project is funded by the Bavarian Ministry of Science and the Arts in the framework of the Bavarian Research Network ‘New Strategies Against Multi-Resistant Pathogens by Means of Digital Net-working – bayresq.net’.


 

 

 

Myeloid cells and adaptive immunity

The SALT is composed of the following main components: I) A complex group of myeloid cell subtypes capable of processing, and presenting skin-derived antigens (foreign or self); II) Skin-draining lymph nodes that respond to cutaneous antigens. III) A wide range of specialized T- and B lymphocytes with different functions.

In this context we are interested in the characterization of dermal-derived antigens within skin-draining lymph nodes. Various mouse models, that are established at the LIT, will help us to specifically detect and analyze migratory dermal cells within skin-draining lymph nodes.

Previous work has demonstrated that certain subtypes of dendritic cells (DC) can induce DC-specific immune responses against pathogens. Using state of the art methods, such as single-cell RNA sequencing and imaging techniques, we aim to decode the cellular mechanisms, responsible for the dissection of commensal- or pathogen-derived immune responses.

The findings will help us to further elucidate the origin and outcome of adaptive immune responses. In addition, myeloid cells with chimeric antigen receptors (CARs) will be developed. CAR-DCs and CAR-macrophages will be used for acceleration or attenuation of immunopathological processes. These aspects will play a central role in clinical applications where T-cell responses are induced (e.g. vaccination) or modulated (e.g. autoimmunity).

Cooperation partners

  • Prof. Dr. Hinrich Abken, Abteilung für Gen-Immuntherapie, LIT Leibniz-Institut für Immuntherapie, Regensburg, Deutschland
  • Dr. Juliane Merl-Pham, Metabolomics and Proteomics Core (MPC), Helmholtz Zentrum München, Deutschland
  • Dr. Florian Groeber-Becker Fraunhofer-Institut für Silicatforschung ISC Translationszentrum, Würzburg, Deutschland
  • Prof. Dr. Jonathan Jantsch, Uniklinik Köln, Deutschland
  • Prof. Dr. Dr. André Gessner, Institut für Mikrobiologie und Hygiene, UKR, Regensburg
  • Prof. Dr. Diana Dudziak, Universitätsklinikum Erlangen, Deutschland

Staff

Benedikt Nerb (PhD)

Phone:      +49 941 944-18127

E-Mail: benedikt.nerb@ukr.de

Selina Harrer (Master Thesis)

Phone:      +49 941 944-18126

 

Former Lab Members: 

  • Sven Mostböck (PostDoc)
  • Christian Florian (Dr. rer. nat)
  • Nicole Zimara (Dr. rer. nat)
  • Anna Hurst (Dr. med.)
  • Maximilian Schmid (Dr. rer. physiol)
  • Christoph Koch (M.Sc. Biologie)
  • Lukas Ali Prokoph (M.Sc. Biologie)
  • Christina Stricker (M.Sc. Biologie)
  • Dominik Grabski (M.Sc. Biologie)
  • Laura de Jonge (M.Sc. Biologie)
  • Juliüs Dürk (B.Sc. Biologie)
  • Bianky Dufner (B.Sc. Biologie)
  • Tobias Gold (M.Sc. Biologie)

Publications

2021

  • Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells. Delacher M., Simon M., Sanderink L., Hotz-Wagenblatt A., Wuttke M., Schambeck K., Schmidleithner L., Bittner S., Pant A., Ritter U., Hehlgans T., Riegel D., Schneider V., Groeber-Becker F.K., Eigenberger A., Gebhard C., Strieder N., Fischer A., Rehli M., Hoffmann P., Edinger M., Strowig T., Huehn J., Schmidl C., Werner J.M., Prantl L., Brors B., Imbusch C.D., and Feuerer M. Immunity. 2021 Mar 24:S1074-7613(21)00119-9. doi: 10.1016/j.immuni.2021.03.007. Epub ahead of print. PMID: 33789089

2019

  • Enhanced production of pro-inflammatory cytokines and chemokines in Ethiopian cutaneous leishmaniasis upon exposure to Leishmania aethiopica. Chanyalew M, Abebe M, Endale B, Girma S, Tasew G, van Zandbergen G, Ritter U, Gadisa E, Aseffa A, Laskay T. Cytokine. 2020 Sep 17:155289. doi: 10.1016/j.cyto.2020.155289. Online ahead of print.
  • Whole blood-based in vitro culture reveals diminished secretion of pro-inflammatory cytokines and chemokines in visceral leishmaniasis. Gadisa E., Abera A., Chanyalew M., Abebe M., Howe R., Ritter U., Aseffa A., LaskayL. Cytokine. Cytokine. 2020 Aug 19:155246. doi: 10.1016/j.cyto.2020.155246. Online ahead of print.
  • Macrophages and Fibroblasts Differentially Contribute to Tattoo Stability. Strandt H., Voluzan O., Niedermair T., Ritter U., Thalhamer J., Malissen B., Stoecklinger A., Henri S. Dermatology. 2020 Apr 28:1-7. doi: 10.1159/000506540.
  • Leishmaniasis: From Innate and Adaptive Immunity to Vaccine Development “. Edited by H. Korner and U. RitterFrontiers in Immunology. Ebook: ISSN 1664-8714. ISBN 978-2-88963-300-5. DOI 10.3389/978-2-88963-300-5

2019

  • Cathelicidin Contributes to the Restriction of Leishmania in Human Host Macrophages. Crauwels P., Bank E., Walber B., Wenzel U.A., Agerberth B., Chanyalew M., Abebe M., König R., Ritter U., Reiling N., van Zandbergen G. Front. Immunol. 2019 10: 2697.
  • Heat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell-killing capability. Ribechini E., Eckert I., Beilhack A., Du Plessis N., Walzl G., Schleicher U., Ritter U. and Lutz M.-B. JCI Insight., 2019 Jul 11; 4(13): e128664.

2018

  • PI3K: A master regulator of brain metastasis-promoting macrophages/microglia. Blazquez R, Wlochowitz D, Wolff A, Seitz S, Wachter A, Perera-Bel J, Bleckmann A, Beißbarth T, Salinas G, Riemenschneider M-J, Proescholdt M, Evert M, Utpatel K, Siam L, Schatlo B, Balkenho M, Stadelmann C, Schildhaus H-U, Korf U, Reinz E, Wiemann S, Vollmer E, Schulz M, Ritter U, Hanisch U-K, Pukrop T. GLIA. 2018 Oct 25. doi: 10.1002/glia.23485.
  • Zimara N., Menberework C., Abraham A., van Zandbergen G., Lepenies B., Schmid M., Weiss R., Rascle A., Wege A.K, Jantsch J., Schatz V., Brown G.D and Ritter U. Dectin-1 positive dendritic cells expand after infection with Leishmania major parasites and represent promising targets for vaccine development. Frontiers in Immunology. 2018 Feb 26;9:263. doi: 10.3389/fimmu.2018.00263. eCollection.

2017

  • Machado Y., Duinkerken S., Hoepflinger V., Mayr M., Korotchenko E., Kurtaj A., Pablos I., Steiner M., Stoecklinger A., Lübbers J., Schmid M., Ritter U., Scheiblhofer S., Ablinger M., Wally V., Hochmann S., Raninger A.M., Strunk D., van Kooyk Y., Thalhamer J., Weiss R. Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy. J Control Release. 2017 Sep 14;266:87-99. doi: 10.1016/j.jconrel.2017.09.020..

2016

  • Brand A., Singer K., Koehl G.E., Kolitzus M., Schoenhammer G., Thiel A., Matos C., Bruss C., Klobuch S., Peter K., Kastenberger M., Bogdan C., Schleicher U., Mackensen A., Ullrich E., Fichtner-Feigl S., Kesselring R., Mack M., Ritter U., Schmid M., Blank C., Dettmer K., Oefner P.J., Hoffmann P., Walenta S., Geissler E.K., Pouyssegur J., Villunger A., Steven A., Seliger B., Schreml S., Haferkamp S., Kohl E., Karrer S., Berneburg M., Herr W., Mueller-Klieser W., Renner K., Kreutz M. LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells. Cell Metab. 2016 Sep 7. pii: S1550-4131(16)30427-2. doi: 10.1016/j.cmet.2016.08.011
  • Tasew G., Gadisa E., Abera A., Zewude A., Chanyalew M., Aseffa A., Abebe M., Ritter U., van Zandbergen G., Laskay T., Tafess K. In vitro permissiveness of bovine neutrophils and monocyte derived macrophages to Leishmania donovani of Ethiopian isolate. Parasite & Vectors. 2016 Apr 18;9(1):218. doi: 10.1186/s13071-016-1441-5.
  • Schatz V., Strüssmann Y., Mahnke A., Schley G., Waldner M., Ritter U., Wild J., Willam C., Dehne N., Brüne B., McNiff J.M., Colegio O.R., Bogdan C., Jantsch J. Myeloid Cell-Derived HIF-1α Promotes Control of Leishmania major. J Immunol. 2016 Nov 15;197(10):4034-4041. Epub 2016 Oct 17.

 2015

  • Schmid M., Dufner B., Dürk J., Bedal K., Stricker K, Prokoph L.A., Koch C., Wege A.K., Zirpel H., van Zandbergen, G., Ecker R., Boghiu B., Ritter, U., An emerging approach for parallel quantification of intracellular protozoan parasites and host cell characterization using TissueFAXS cytometry. PLOS ONE. 2015. Oct 21;10(10):e0139866. doi: 10.1371/journal.pone.0139866. eCollection 2015.

2014

  • Zimara*, N., Florian*, C., Schmid*, M., Malissen, B., Kissenpfennig, A., Mannel, D. N., Edinger, M., Hutchinson, J. A., Hoffmann, P. and Ritter, U., Langerhans cells promote early germinal center formation in response to Leishmania-derived cutaneous antigens. Eur J Immunol 2014. 44: 2955-2967.* contributed equally. 
  • Schmid, M., Zimara, N., Wege, A. K. and Ritter, U., Myeloid-derived suppressor cell functionality and interaction with Leishmania major parasites differ in C57BL/6 and BALB/c mice. Eur J Immunol 2014. 44: 3295-3306. 
  • Managh, A. J., Hutchinson, R. W., Riquelme, P., Broichhausen, C., Wege, A. K., Ritter, U., Ahrens, N., Koehl, G. E., Walter, L., Florian, C., Schlitt, H. J., Reid, H. J., Geissler, E. K., Sharp, B. L. and Hutchinson, J. A., Laser ablation-inductively coupled plasma mass spectrometry: an emerging technology for detecting rare cells in tissue sections. J Immunol 2014. 193: 2600-2608. 

2012 

  • Scheiblhofer, S., Ritter, U. , Thalhamer, J. and Weiss, R., Protein antigen delivery by gene gun-mediated epidermal antigen incorporation (EAI). Methods Mol Biol 2013. 940: 401-411. 
  • Wenzel, U. A., Bank, E., Florian, C., Forster, S., Zimara, N., Steinacker, J., Klinger, M., Reiling, N., Ritter, U. and van Zandbergen, G., Leishmania major parasite stage-dependent host cell invasion and immune evasion. FASEB J 2012. 26: 29-39. 
  • Wege, A. K., Florian, C., Ernst, W., Zimara, N., Schleicher, U., Hanses, F., Schmid, M. and Ritter, U., Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response. PLoS Negl Trop Dis 2012. 6: e1741. 
  • Schmid, M., Wege, A. K. and Ritter, U. , Characteristics of "Tip-DCs and MDSCs" and Their Potential Role in Leishmaniasis. Front Microbiol 2012. 3: 74. 

2011

  • Kolbaum, J., Ritter, U. , Zimara, N., Brewig, N., Eschbach, M. L. and Breloer, M., Efficient control of Leishmania and Strongyloides despite partial suppression of nematode-induced Th2 response in co-infected mice. Parasite Immunol 2011. 33: 226-235. 
  • Florian, C., Barth, T., Wege, A. K., Mannel, D. N. and Ritter, U., An advanced approach for the characterization of dendritic cell-induced T cell proliferation in situ. Immunobiology 2011. 215: 855-862. 

 2010

  • Ritter U. Presentation of skin-derived Leishmania antigen by dendritic cell subtypes [Book chapter, Protozoa, Immune Response to Parasitic Infections Vol-1. October 2010. Bentham-Press ; pp 123-136.

 2009

  • Ritter, U. , Frischknecht, F. and van Zandbergen, G., Are neutrophils important host cells for Leishmania parasites? Trends Parasitol2009. 25: 505-510.
  • Horst, A. K., Bickert, T., Brewig, N., Ludewig, P., van Rooijen, N., Schumacher, U., Beauchemin, N., Ito, W. D., Fleischer, B., Wagener, C. and Ritter, U ., CEACAM1+ myeloid cells control angiogenesis in inflammation. Blood 2009. 113: 6726-6736.
  • Commented by A.M. Randi and B. Bussolati. Blood. 2009 Jun 25;113(26):6508-10.
  • Brewig, N., Kissenpfennig, A., Malissen, B., Veit, A., Bickert, T., Fleischer, B., Mostbock, S. and Ritter, U. Priming of CD8+ and CD4+ T cells in experimental leishmaniasis is initiated by different dendritic cell subtypes. J Immunol2009. 182: 774-783.

2008

  • Ritter, U . Lechner, A., Scharl, K., Kiafard, Z., Zwirner, J. and Korner, H., TNF controls the infiltration of dendritic cells into the site of Leishmania major infection. Med Microbiol Immunol2008. 197: 29-37.

 2007

  • Weiss, R., Scheiblhofer, S., Thalhamer, J., Bickert, T., Richardt, U., Fleischer, B. and Ritter, U.  Epidermal inoculation of Leishmania-antigen by gold bombardment results in a chronic form of leishmaniasis. Vaccine2007. 25: 25-33.
  • Ritter, U. and Osterloh, A. A new view on cutaneous dendritic cell subsets in experimental leishmaniasis. Med Microbiol Immunol 2007. 196: 51-59. Commented by J. Moreno. Trends in Parasitology. 2007. Mar;23(3):86-8.
  • Breloer, M., Kretschmer, B., Luthje, K., Ehrlich, S., Ritter, U. , Bickert, T., Steeg, C., Fillatreau, S., Hoehlig, K., Lampropoulou, V. and Fleischer, B., CD83 is a regulator of murine B cell function in vivo. Eur J Immunol 2007. 37: 634-648.

 2004

  • Ritter, U. , Meissner, A., Scheidig, C. and Korner, H., CD8 alpha- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis. Eur J Immunol 2004. 34: 1542-1550.
  • Ritter, U. , Mattner, J., Rocha, J. S., Bogdan, C. and Korner, H., The control of Leishmania (Leishmania) major by TNF in vivo is dependent on the parasite strain. Microbes Infect 2004. 6: 559-565.
  • Hebeis, B. J., Klenovsek, K., Rohwer, P., Ritter, U ., Schneider, A., Mach, M. and Winkler, T. H., Activation of virus-specific memory B cells in the absence of T cell help. J Exp Med 2004. 199: 593-602.

2003

  • Meissner, A., Zilles, O., Varona, R., Jozefowski, K., Ritter, U. , Marquez, G., Hallmann, R. and Korner, H., CC chemokine ligand 20 partially controls adhesion of naive B cells to activated endothelial cells under shear stress. Blood 2003. 102: 2724-2727.

 2002

  • Wilhelm, P., Riminton, D. S., Ritter, U ., Lemckert, F. A., Scheidig, C., Hoek, R., Sedgwick, J. D. and Korner, H., Membrane lymphotoxin contributes to anti-leishmanial immunity by controlling structural integrity of lymphoid organs. Eur J Immunol 2002. 32: 1993-2003.
  • Ritter, U. and Korner, H., Divergent expression of inflammatory dermal chemokines in cutaneous leishmaniasis. Parasite Immunol 2002. 24: 295-301.

 2001

  • Wilhelm, P., Ritter, U. , Labbow, S., Donhauser, N., Rollinghoff, M., Bogdan, C. and Korner, H., Rapidly fatal leishmaniasis in resistant C57BL/6 mice lacking TNF. J Immunol2001. 166: 4012-4019.

 2000

  • Ritter, U. and Moll, H., Monocyte chemotactic protein-1 stimulates the killing of leishmania major by human monocytes, acts synergistically with IFN-gamma and is antagonized by IL-4. Eur J Immunol2000. 30: 3111-3120.

1996

  •  Ritter, U ., Moll, H., Laskay, T., Brocker, E., Velazco, O., Becker, I. and Gillitzer, R., Differential expression of chemokines in patients with localized and diffuse cutaneous American leishmaniasis. J Infect Dis1996. 173: 699-709.
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