Hauser lab

Investigating the interaction of immune cells in living tissue

Introduction
Members
Cooperation partners
Selected publications
Third party funding projects

Immune Dynamics

We are interested in determining how immune cells behave in the tissue context, how they interact with other immune cells as well as with various cell types in the tissues they reside in, and how that shapes immune responses. We aim to dissect how the behavior of various immune cell subsets in various tissues affects processes such as chronic inflammation, which occurs in the course of rheumatic diseases.

One focus of our lab is analyzing the biology of long lived plasma cells. As the producers of antibodies, they play a crucial role in immunological memory, securing life-long protective immune responses. The longevity of plasma cells depends on their microenvironment, which provides survival factors in tissue niches of the bone marrow. We could identify bone marrow stromal cells acting as stable components of these niches. They attract plasma cells to the bone marrow niches by secretion of CXCL12. The numbers of these stromal niche organizers remain stable during the course of an immune response, thereby limiting the number of available niches to the plasma cells, which migrate from secondary lymphoid organs to the bone marrow to become long lived. In contrast, eosinophils, which provide the survival factor APRIL to plasma cells, are transient niche inhabitants. In order to further characterize the cellular dynamics in the bone marrow niches, we have developed a microendoscopic implant which allows us to analyze cellular migration and interactions in the bone marrow over months by intravital microscopy. This technology gives us new insights into what is happening in this tissue. For example, we have been able to show that the blood vessels surrounding and supplying bone marrow niches are highly dynamic and are constantly remodelled. We are now investigating the consequences of these changes on the composition of the niches.

Furthermore, we could show that plasma cells in the small intestine can also become long lived, and that the microenvironment of the gut provides similar survival signals to them as the bone marrow, although the cell types that produce these factors differ between tissues. Interestingly, plasma blasts generated in mucosal immune responses can also contribute to the long-lived plasma cell pool in the bone marrow.

Besides their crucial functions in protective immunity, long lived plasma cells also contribute to autoimmune diseases by secreting autoreactive antibodies that can mediate tissue destruction and the perpetuation of chronic inflammation. Using experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis, we recently demonstrated that the chronically inflamed central nervous system also provides niches for long lived plasma cells. In line with that, non-proliferative plasma cells could be found in biopsies derived from the CNS of multiple sclerosis patients. Hence, under the conditions of chronic inflammation, niches for immune memory can form even in organs that are void of immune cells in healthy individuals. A better understanding of the mechanisms underlying the formation and maintenance of those niches is crucial to therapeutically target pathogenic plasma cells.

Group Leader
    Prof. Dr. med. vet. Anja Erika Hauser

Prof. Dr. med. vet. Anja Erika Hauser

Department of Rheumatolgoy and Clinical Immunology
Charité – Universitätsmedizin Berlin
anja.hauser-hankeln@charite.de

Deutsches Rheuma-Forschungszentrum Berlin
Immunodynamics
Charitéplatz 1
10117 Berlin
Gemany

Phone +49 (0)30 28460-784
Fax +49 (0)30 28460-603
hauser@drfz.de

Keywords
Multiphoton microscopy
Plasma cells
Confocal microscopy
Hhistocytometry
Chronic inflammation

Continue to Members

Group leader
Prof. Dr. med. vet. Anja Hauser

Scientists
Randall Lindquist, PhD
Dr. rer. nat. Karolin Pollok
Dr. rer. nat. Anna Pascual-Reguant

PhD students
Carolin Ulbricht,
Karolin Holzwarth,
Jonathan Stefanowski

Bachelor/Diploma/Master students
Sven Flatow, Sylvia Uhlmann, Veronika Raba

Technicians
Robert Günther, Ralf Uecker

MD -Students
Ronja Mothes, Raphael Raspe, Lennard Ostendorf

Students
Alina Liebheit

Microscope Operator
Ralf Köhler

Group Leader
    Prof. Dr. med. vet. Anja Erika Hauser

Prof. Dr. med. vet. Anja Erika Hauser

Department of Rheumatolgoy and Clinical Immunology
Charité – Universitätsmedizin Berlin
anja.hauser-hankeln@charite.de

Deutsches Rheuma-Forschungszentrum Berlin
Immunodynamics
Charitéplatz 1
10117 Berlin
Gemany

Phone +49 (0)30 28460-784
Fax +49 (0)30 28460-603
hauser@drfz.de

Keywords
Multiphoton microscopy
Plasma cells
Confocal microscopy
Hhistocytometry
Chronic inflammation

Continue to Cooperation partners
  • E. Esplugues, Yale University School of Medicine, New Haven, CT, USA
  • M.-T. Figge, Applied Systems Biology, HKI Jena, Germany
  • K.D. Fischer, Institute for Biochemistry and Cell Biology; Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120, Magdeburg
  • R. A. Manz, Universität zu Lübeck, Institut für systemische Entzündungsforschung (ISEF), Ratzeburger Allee 160, 23562 Lübeck
  • Kai-Michael Toellner, Institute of Immunology and Immunotherapy, Medical School/IBR, University of Birmingham, Birmingham, UK
  • H. Radbruch, Institut für Neuropathologie, Charité – Universitätsmedizin, Charitéplatz 1, 10117 Berlin
  • C. Wählby, Department of Information Technology, Centre for Image Analysis, Uppsala University, Uppsala, Sweden
Group Leader
    Prof. Dr. med. vet. Anja Erika Hauser

Prof. Dr. med. vet. Anja Erika Hauser

Department of Rheumatolgoy and Clinical Immunology
Charité – Universitätsmedizin Berlin
anja.hauser-hankeln@charite.de

Deutsches Rheuma-Forschungszentrum Berlin
Immunodynamics
Charitéplatz 1
10117 Berlin
Gemany

Phone +49 (0)30 28460-784
Fax +49 (0)30 28460-603
hauser@drfz.de

Keywords
Multiphoton microscopy
Plasma cells
Confocal microscopy
Hhistocytometry
Chronic inflammation

Continue to Selected publications
  1. Reismann D.*, J. Stefanowski*, R. Guenther, A. Rakhymzhan, R. Matthys, R. Nützi, S. Zehentmeier, K. Schmidt-Bleek, G. Petkau, H.D. Chang, S. Naundorf, Y. Winter, F. Melchers, Duda, G., E. Hauser* and R. Niesner*. 2017. Longitudinal intravital imaging of the femoral bone marrow reveals plasticity within marrow vasculature. Nature Commun 8: 2153 *equal contribution
  2. Pollok, K., R. Mothes, C. Ulbricht, A. Liebheit, J. D. Gerken, S. Uhlmann, F. Paul, R. Niesner, H. Radbruch, and E. Hauser. 2017. The chronically inflamed central nervous system provdes niches for long-lived plasma cells. Acta Neuropathol Commun 5: 88.
  3. Radbruch, H., R. Mothes, D. Bremer, S. Seifert, J. Pohlan, L. Ostendorf, R. Guenther, R. Leben, W. Stenzel, R. Niesner, and E. Hauser. 2017. Analyzing NADPH-oxidase activation in aging and vascular amyloid pathology. Frontiers Immunol. 8:844
  4. Pascual-Reguant, A., J. Bayat Sarmadi, C. Baumann, R. Noster, D. Cirera-Salinas, C. Curato, P. Pelczar, S. Huber, C. E. Zielinski, M. Lohning, E. Hauser*, and E. Esplugues*. 2017. TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine. Mucosal Immunol. 10: 1431-1442 *equal contribution
  5. Lemke, A.*, M. Kraft*, K. Roth, R. Riedel, D. Lammerding, and E. Hauser. 2016. Long-lived plasma cells are generated in mucosal immune responses and contribute to the bone marrow plasma cell pool in mice. Mucosal Immunol. 9: 83-97. *equal contribution
Group Leader
    Prof. Dr. med. vet. Anja Erika Hauser

Prof. Dr. med. vet. Anja Erika Hauser

Department of Rheumatolgoy and Clinical Immunology
Charité – Universitätsmedizin Berlin
anja.hauser-hankeln@charite.de

Deutsches Rheuma-Forschungszentrum Berlin
Immunodynamics
Charitéplatz 1
10117 Berlin
Gemany

Phone +49 (0)30 28460-784
Fax +49 (0)30 28460-603
hauser@drfz.de

Keywords
Multiphoton microscopy
Plasma cells
Confocal microscopy
Hhistocytometry
Chronic inflammation

Continue to Third party funding projects
  • Analysis of B cell dynamics in chronic neuroinflammation, DFG CRC130 B cells-immunity and autoimmunity; project 17, Anja Hauser, 2013-2017 (first funding period) 2017-2021 (second funding period)
  • Longitudinal Multi-Photon Microscopy and Microendoscopy: Quantifying and controlling Communication and Function of B Lymphocytes in vivo, DFG CRC130 B cells-immunity and autoimmunity; project C01; Anja Hauser 2017-2021 (second funding period)
  • Analyzing the Heterogeneity of Innate Lymphoid Cells and the Relationship with their Microenvironments in situ and in vivo, DFG SPP1937 Innate lymphoid cells (HA5354/8-1)
  • Longitudinal intravital imaging of dynamics of osteo-immunological interactions during bone healing, project 7 within DFG FOR 2165 “Regeneration in Aged Individuals: Using bone healing as a model system to characterize regeneration under compromised conditions“; 2015-2018 (first funding period) 2018-21 (second funding period) (HA5354/6-1)
  • Junior Group Neuroimmunology, Cluster of Excellence NeuroCure, DFG EXC257 NeuroCure 2013-2017
Group Leader
    Prof. Dr. med. vet. Anja Erika Hauser

Prof. Dr. med. vet. Anja Erika Hauser

Department of Rheumatolgoy and Clinical Immunology
Charité – Universitätsmedizin Berlin
anja.hauser-hankeln@charite.de

Deutsches Rheuma-Forschungszentrum Berlin
Immunodynamics
Charitéplatz 1
10117 Berlin
Gemany

Phone +49 (0)30 28460-784
Fax +49 (0)30 28460-603
hauser@drfz.de

Keywords
Multiphoton microscopy
Plasma cells
Confocal microscopy
Hhistocytometry
Chronic inflammation

Continue to Introduction