Immune Dynamics

Using advanced microscopy to understand the interplay of immune cells in the living organism

Hauser

Introduction

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 recently developed a microendoscopic implant which allows us to analyze cellular  migration and interactions in the bone marrow over months by intravital microscopy.

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.

Selected Publications

TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine. Pascual-Reguant A, Bayat Sarmadi J, Baumann C, Noster R, Cirera-Salinas D, Curato C, Pelczar P, Huber S, Zielinski CE, Löhning M, Hauser AE, Esplugues E. *equally contributing senior authors. Mucosal Immunol. 2017 Feb 15. doi: 10.1038/mi.2017.5.

Herrtwich, L., I. Nanda, K. Evangelou, T. Nikolova, V. Horn, Sagar, D. Erny, J. Stefanowski, L. Rogell, C. Klein, K. Gharun, M. Follo, M. Seidl, B. Kremer, N. Munke, J. Senges, M. Fliegauf, T. Aschman, D. Pfeifer, S. Sarrazin, M. H. Sieweke, D. Wagner, C. Dierks, T. Haaf, T. Ness, M. M. Zaiss, R. E. Voll, S. D. Deshmukh, M. Prinz, T. Goldmann, C. Holscher, A. E. Hauser, A. J. Lopez-Contreras, D. Grun, V. Gorgoulis, A. Diefenbach, P. Henneke, and A. Triantafyllopoulou. 2016. DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas. Cell 167: 1264-1280 e1218.

Radbruch, H., D. Bremer, R. Guenther, Z. Cseresnyes, R. Lindquist, A. E. Hauser, and R. Niesner. 2016. Ongoing Oxidative Stress Causes Subclinical Neuronal Dysfunction in the Recovery Phase of EAE. Frontiers in immunology 7: 92

Lemke, A., M. Kraft, K. Roth, R. Riedel, D. Lammerding, and A. 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.

Automated quantification of hematopoietic cell - stromal cell interactions in histological images of undecalcified bone. Zehentmeier S, Cseresnyes Z, Escribano Navarro J, Niesner RA, Hauser AE. J Vis Exp. 2015 Apr 8;(98). doi: 10.3791/52544.

Members

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

Scientists
Dr. Sandra Zehentmeier
Dr. Randall Lindquist
Dr. Karolin Pollok

PhD students
Carolin Ulbricht
Jonathan Stefanowski
Karolin Holzwarth
Laura Tech
Jannike Bayat Sarmadi
Anna Pascual

MD students
Agata Mossakowski
Magdalena Kraft
Dominik Lammerding
Julian Pohlan
Lennard Ostendorf

Bachelor/Diploma/Master students
Veronica Raba
Sylvia Uhlmann
Sven Flatow
Alina Liebheit
Fabian Kriegel

Technicians
Robert Günther
Ralf Uecker

Microscope Operator
Ralf Köhler

Student
Markus Köhler

Cooperation partners

Dr. G. Duda, Charité, Justus-Wolff-Institut, Berlin, Germany

Dr. H. Radbruch, Charité, Institut für Neuropathologie, Berlin, Germany

Dr. E. Esplugues, Yale University School of Medicine, New Haven, CT, USA

Prof. M.-T. Figge, Applied Systems Biology, HKI Jena, Germany

PD Dr. U. Höpken, MDC Berlin, Germany

Prof. K.-M. Toellner, University of Birmingham, Institute of Immunology and Immunotherapy,Birmingham, United Kingdom

Dr. A. Triantafyllopoulou, Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg, Germany

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 28460-238
Fax +49 (0)30 28460-603
hauser@drfz.de

Keywords
Multiphoton microscopy
Plasma cells
Confocal microscopy
Hhistocytometry
Chronic inflammation

Radbruch Prof. Dr. rer. nat. Andreas Radbruch Cell Biology Triantafyllopoulou_klein Dr. Antigoni Triantafyllopoulou Innate Immunity in Rheumatic Diseases Thurley Dr. Kevin Thurley Systems Biology of inflammation Ahmed Hegazy Dr. med. Dr. rer. nat. Ahmed N. Hegazy Inflammatory Mechanisms Polansky Dr. Julia Polansky-Biskup Immuno-Epigenetics Melchers Prof. Dr. Fritz Melchers Lymphocyte Development Farzin Mashreghi Dr. Mir-Farzin Mashreghi Therapeutic Gene Regulation Kruglov Dr. rer. nat. Andrey Kruglov Chronic Inflammation Loehning Prof. Dr. Max Löhning Pitzer Lab Osteoarthritis Research Kubagawa Prof. Dr. Hiromi Kubagawa Humoral Immune Regulation Hauser Prof. Dr. med. vet. Anja Erika Hauser Immune Dynamics Tokoyoda Dr. Koji Tokoyoda Osteoimmunology Scheffold Prof. Dr. rer. nat. Alexander Scheffold Cellular Immunology Niesner Dr. rer. nat. Raluca Niesner Biophysical Analytics Strangfeld Dr. med. Anja Strangfeld Pharmacoepidemiology Minden Prof. Dr. med. Kirsten Minden Paediatric Rheumatology Listing Dr. Joachim Listing Statistics & Clinical Studies Angela_Zink_230x230 Prof. Dr. Angela Zink Health Services Research Worm Prof. Dr. med. Margitta Worm Allergology Poddubnyy Prof. Dr. Denis Poddubnyy Spondyloarthritides Riemekasten Prof. Dr. med. Gabriela Riemekasten Cell Autoimmunity Hiepe Prof. Dr. med. Falk Hiepe Autoimmunology Hamann Prof. Dr. rer. nat. Alf Hamann Experimental Rheumatology Doerner Prof. Dr. med. Thomas Dörner B Cell Memory Buttgereit Prof. Dr. med. Frank Buttgereit Glucocorticoids & Bioenergetics Romagnani Prof. Dr. Chiara Romagnani Innate Immunity Hutloff Dr. rer. nat. Andreas Hutloff Chronic Immune Reactions Fillatreau Prof. Dr. rer. nat. Simon Fillatreau Immune Regulation Baumgrass Prof. Dr. Ria Baumgrass Signal Transduction Nedospasow Prof. Dr. Sergei Nedospasov Inflammation Biology