Laboratory of Translational Immunology
The current focus of our laboratory is to better characterize the factors that shape antibody-dependent innate immune cell responses and to predict the effect of monoclonal antibody (mAb) therapies in the setting of autoimmunity. The cellular crosstalk/interactions between innate immune cells during the clearance of Ab-coated target cells are explored. This involves the use of conventional static assays and a novel 3D micro-vessels system using a pulsatile flow system mimicking intravascular conditions. With this, we aim to follow the 3R principle. Our ultimate goal is to have a better understanding of the pathophysiology of innate immune responses triggered by IgG–FcγR interactions in Ab-associated autoimmune pathologies and following therapeutic mAb applications, i.e. ADCC and ADPC. This approach might allow us to better predict the efficiency of therapeutic mAb in individual patients. Finally, elucidating the molecular mechanism of the crosstalk among innate immune cells might lead to the generation of novel therapeutic hypotheses and strategies.
Translation and Clinical Immunology. As clinician, I have been constantly challenged by the clinical practice, and as product of my curiosity, I have the opportunity to contribute to several aspects of clinical immunology from early in my career, for instance, the value of simple neutrophil left shift as a predictor of inflammatory and infectious disease; risk factors at intensive care unit after hematopoietic stem cells transplantation, diagnostics and treatment of rare autoinflammatory and autoimmune pathologies or the role of immune deficiency in patients with as well as taking part in retrospective and prospective clinical studies.
Previously, my interest was focused on interactions between human NK cells and porcine endothelial cells (pEC) in the field of Xenotransplantation. My collaborators and I contributed to several important aspects of NK cell activation, inhibition, and function during xenorejection. We demonstrated that ADCC against pEC mediated by human NK cells in the presence of xenoreactive Abs is not affected by the blocking of activating NK receptors. Direct NK cytotoxicity of pEC depended predominantly on the perforin/Grz B pathway, was triggered by the activating receptors NKp44 and NKG2D, but not by NKp30 and NKp46. Later on we explored the potential of regulatory cells including Treg subpopulations and tolerogenic DC to prevent transplant rejection.
Finally, in recent years we demonstrated the effect of immunosuppressive drugs and therapeutic immunoglobulins on NK cytotoxicity including ADCC, we gained a vast experience in functional assays for ADCC, ADCP and cytokine production by innate immune cells triggered by FcR engagement showing the differential effects of IgG subclasses.
Seebach JD, Morant R, Rüegg R, Seifert B, Fehr J. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am. J. Clin. Pathol. 1997; 107:582-591
Weiss E*, Lilienfeld B*, Müller S, Müller E, Herbach N, Kessler B, Wanke R, Schwinzer R, Seebach JD*, Wolf E*, Brem G*. HLA-E/human 2-microblobulin transgenic pigs: protection agains xenogeneic human anti-pig natural killer cell cytotoxicity. Transplantation 2009;87;1:3543
Muller YD, Golshayan D, Ehirchiou D, Wass JC, Giovannoni L, Meier R, Serre-Beinier V, Puga Yung G, Morel P, *Bühler L, *Seebach JD. Immunosuppressive effects of streptozotocin-induces diabetes result in absolute lymphopenia and a relative of T regulatory cells. Diabetes 2011 60:2331-2340
Schwitzguébel AJ, Jandus P, Lacroix J-S, *Seebach JD, *Harr T. Immunoglobulin deficiency in chronic rhinosinusitis: systematic review of the literature and meta-analysis. *Both last authors contributed equally to this work. J Allergy Clin Immunol. 2015;136:1523-31
Papaserafeim M, Jandus P, Ferfoglia RI, Nieke JP, Vonarburg C, Spirig R, Yung GP, Seebach JD. Effect of intravenous immunoglobulin G therapy on natural killer cell function related to Fc gamma receptor gene expression. J Allergy Clin Immunol. 2020:S0091-6749(20)30485-1October 28, 2020