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.
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.
Prof. Dr. med. vet. Anja Erika Hauser
Dr. Sandra Zehentmeier
Dr. Randall Lindquist
Dr. Karolin Pollok
Jannike Bayat Sarmadi
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