Zeißig - Mucosal Immunology


Sebastian Zeißig

1998-2004  Medical studies, Charité Berlin, Campus Benjamin Franklin, Berlin, Germany

2004 M.D., Charité, Campus Benjamin Franklin, Berlin, Germany

2005 M.D. Thesis, Department of Gastroenterology, Charité, Berlin, Germany

2004-2005 DFG Research Training Group 276/3, Charité Berlin, Germany

2005-2006 Postdoctoral fellow, Charité Berlin, Germany 

2006-2010 Postdoctoral fellow, Harvard Medical School, Boston, MA

2012-2015 Assistant professor for “Immunological aspects of intestinal barrier diseases”, Christian-Albrechts-University Kiel, Germany 

Since 2015 Associate professor for "Molecular Gastroenterology", Department of Medicine I and Center for Regenerative Therapies Dresden, Technical University Dresden

Previous and current research

We are interested in the immunological mechanisms underlying inflammation and inflammation-associated tumorigenesis in the intestine and the liver, with a particular focus on translational research in inflammatory bowel disease and basic research aiming towards a better understanding of the role of lipids in immunity.

Lipid antigens in immunity

Chronic inflammation and tissue destruction are the basis for inflammatory bowel diseases (IBD) and autoimmune as well as viral hepatitis. These diseases are not only associated with debilitating clinical symptoms but are also key risk factors for the development of inflammation-associated malignancy. The development of novel therapeutic strategies that target these diseases is dependent on a detailed understanding of the cellular and molecular mechanisms underlying chronic inflammation. Of particular interest in this regard is the role of natural killer T (NKT) cells, an unconventional subset of T cells that responds to CD1d-restricted presentation of self and foreign lipid antigens and is associated with immediate innate-like effects on NK, T, and B cells thereby shaping and orchestrating immune responses. NKT cells are critical for antimicrobial immunity and genetic defects in lipid antigen presentation are associated with primary immunodeficiency in humans. However, recent studies have revealed that NKT cells are not only contributing to protective immunity but also play central roles in the pathogenesis of chronic inflammatory disorders. Thus, it was shown that ulcerative colitis, an inflammatory bowel disease (IBD), is characterized by NKT cell-dependent intestinal inflammation. Similarly, recent studies have revealed that NKT cells are centrally involved in the pathogenesis of autoimmune and infectious hepatitis.

In our recent work investigating the role of lipid antigens and NKT cells in intestinal and hepatic immunity, we could demonstrate that hepatocytes and intestinal epithelial cells can present lipid antigens via the non-classical MHC class I molecule CD1d to natural killer T cells thus providing the basis for protection from infectious hepatitis as well as intestinal inflammation (Zeissig et al., Nat. Med. 2012; Olszak et al., Nature 2014). Furthermore, this work revealed an essential role of the commensal microbiota and microbiota-derived lipid antigens in the control of homeostasis at mucosal surfaces and demonstrated that primary defects in lipid antigen presentation are associated with immunodeficiency in humans (An et al., Cell 2014; Olszak et al., Science 2012; Zeissig et al., J. Clin. Invest.; Zeissig et al., Nat. Immunol. 2014). Current ERC-funded work in the laboratory (ERC Starting Grant) is focused on the identification of lipid antigens which link metabolism and immunity in the liver and the intestine. 

Monogenic forms of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of disorders characterized by chronic intestinal and often systemic inflammation. In the vast majority of IBD patients, intestinal inflammation occurs through a complex and incompletely understood interplay of genetic and environmental factors. However, we and others have recently identified forms of mono- or oligogenic forms of IBD, in which one or few genetic defects significantly promote intestinal inflammation (Zeissig Y, Gut 2014; Zeissig S, Gut 2014). Patients with monogenic IBD often present with early-onset disease manifesting during childhood and exhibit severe and often treatment-refractory intestinal and systemic inflammation. The identification of a mono- or oligogenetic etiology in IBD patients thereby provided significant insight into the pathophysiology of IBD and forced, in a subset of these cases, a reconsideration of approaches for medical treatment. This translational research agenda is pursued in close collaboration with the Department of Pediatrics (Prof. Dr. Berner, Dr. Laaß) and the Institute of Clinical Molecular Biology (IKMB) Kiel (Prof. Dr. Schreiber, Prof. Dr. Franke). Genetic screening is offered to patients with early onset and/or familial IBD.

Group Members

List of group members

 

Selected Publications

Zeissig Y, Petersen, BS, Milutinovic S, Bosse E, Mayr G, Peuker K, Keller A, Kohl M, Laass M, Billmann-Born S, Brandau H, Feller AC, Röcken C, Schrappe M, Rosenstiel P, Reed JC, Schreiber S, Franke A, Zeissig S. XIAP variants associated with NOD1/2 dysfunction in pediatric-onset Crohn’s disease. Gut 2015 Jan;64(1):66-76.

Olszak T, Neves JF, Dowds CM, Baker K, Glickman J, Davidson NO, Lin CS, Jobin C, Brand S, Sotlar K, Wada K, Katayama K, Nakajima A, Mizuguchi H, Kawasaki K, Nagata K, Müller W, Snapper SB, Schreiber S, Kaser A, Zeissig S*, Blumberg RS*.  Protective mucosal immunity mediated by epithelial CD1d and IL-10. Nature. 2014 May 22;509(7501):497-502.  (*co-senior authors)

Zeissig S, Petersen BS, Tomczak M, Melum E, Huc-Claustre E, Dougan SK, Laerdahl JK, Stade B, Forster M, Schreiber S, Weir D, Leichtner AM, Franke A, Blumberg RS. Early-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4. Gut. 2014 Nov 3.

Zeissig S, Blumberg RS. Life at the beginning: perturbation of the microbiota by antibiotics in early life and its role in health and disease. Nat. Immunol. 2014 Mar 19; 15(4): 307-10.

An D, Oh SF, Olszak T, Neves JF, Erturk-Hasdemir D, Lu X, Zeissig S, Blumberg RS, Kasper DL. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell. 2014 Jan 16;156(1-2): 123-33.

Heap GA, Weedon MN, Bewshea CM, Singh A, Chen M, Satchwell JB, Vivian JP, So K, Dubois PC, Andrews JM, Annese V, Bampton P, Barnardo M, Bell S, Cole A, Connor SJ, Creed T, Cummings FR, D'Amato M, Daneshmend TK, Fedorak RN, Florin TH, Gaya DR, Greig E, Halfvarson J, Hart A, Irving PM, Jones G, Karban A, Lawrance IC, Lee JC, Lees C, Lev-Tzion R, Lindsay JO, Mansfield J, Mawdsley J, Mazhar Z, Parkes M, Parnell K, Orchard TR, Radford-Smith G, Russell RK, Reffitt D, Satsangi J, Silverberg MS, Sturniolo GC, Tremelling M, Tsianos EV, van Heel DA, Walsh A, Watermeyer G, Weersma RK, Zeissig S, Rossjohn J, Holden AL; International Serious Adverse Events Consortium; IBD Pharmacogenetics Study Group, Ahmad T. HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. Nat Genet. 2014 Oct;46(10):1131-4.

Zeissig S, Murata M, Sweet L, Publicover J, Hu Z, Kaser A, Bosse E, Iqbal J, Hussain MM, Balschun K, Röcken C, Arlt A, Günther R, Hampe J, Schreiber S, Baron JL, Moody DB, Liang JT, Blumberg RS. Hepatitis B virus-induced alterations in hepatocyte CD1d lipid antigens activate natural killer T cells and contribute to protective immunity. Nat. Med. 2012. Jul;18(7):1060-8.

Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, Glickman JN, Siebert R, Baron RM, Kasper DL, Blumberg RS. Microbial exposure during early life has persistent effects on tissue-associated iNKT cells and their function. Science. 2012 Apr 27;336(6080):489-93.

Zeissig S, Dougan SK, Barral D, Junker Y, Chen Z, Kaser A, Ho M, Mandel H, McIntyre A, Kennedy SM, Painter, GF, Veerapen N, Besra GS, Cerundolo V, Yue S, Beladi S, Behar SM, Chen X, Gumpertz JE, Breckpot K, Raper A, Baer A, Exley MA, Hegele RA, Cuchel M, Rader DJ, Davidson NO, Blumberg RS, Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function. J Clin Invest. 2010 Aug 2;120(8):2889-99.

Last Modified: 26/05/2016