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Cellular and Molecular Regulation of Immunity in Barrier Organs Friday 27Th November 2015, Munich

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Cellular and Molecular Regulation of Immunity in Barrier Organs Friday 27Th November 2015, Munich SFB 1054 International Symposium CELLULAR AND MOLECULAR REGULATION OF IMMUNITY IN BARRIER ORGANS Friday 27th November 2015, Munich With generous support by: SFB 1054 Control and Plasticity of Cell-Fate Decisions in the Immune System CELLULAR AND MOLECULAR SFB 1054 REGULATION OF IMMUNITY IN BARRIER ORGANS Dear SFB members, dear guests, Imprint I would like to welcome you to the symposium „Cellular and molecular regulation of immunity in barrier organs“ organized by our Collaborative Research Center (SFB 1054). Immune cells SFB 1054 Office in epithelial barrier organs, such as skin, lung and intestine are constantly exposed to microbial Institute for Immunology and environmental factors, which shape their development and function in a tissue-specific Ludwig-Maximilians-Universität München manner. Dendritic cells, macrophages, innate lymphoid cells and T cells are critically involved in Goethestr. 31 tissue homeostasis and immune defense in these organs. High-throughput siRNA and CRISPR/ 80336 München Cas9 technologies have opened the door to discovery of molecules with previously unknown function which play central roles in the development and activity of these immune cell types in Phone: +49 (0)89 2180-75680 / -75669 their specific tissue environment. E-Mail: [email protected] For this symposium, which is financed by the German Research Foundation gender equality funds, we invited six accomplished female immunologists, who are leading researchers in this field. Our aim is to encourage our female PhD students and postdocs to further pursue a scientific career and to increase the number of women in leading positions in Immunology. Universities and other research institutions face the challenge to attract and retain more women in science. Recent studies identify measures, which may help to achieve this goal. The speakers will share their own experiences and discuss these issues with SFB members. Anne Krug (SFB 1054) 2 3 Program SFB 1054 10:00 – 12:00 Round table discussion Lecture Hall F 1.20 Session 2 Chair: Anne Krug Lecture Hall F 1.08 Gender Equality and Science (moderation by CLPM, LMU) 16:00 – 16:30 n Christina Zielinski 12:00 – 13:00 Lunch Room D 0.30 Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich Session 1 Chair: Thomas Brocker Lecture Hall F 1.08 Regulation of pro- and anti-inflammatory human T cell properties in health and inflammation 13:00 – 13:15 Anne Krug (SFB 1054) – Welcome adress 16:30 – 17:00 n Chiara Romagnani Barbara Conradt (LMU vice president) – Welcome adress Deutsches Rheuma Forschungszentrum, Berlin Activation and differentiation of human innate lymphoid cells 13:15 – 13:45 n Irmgard Förster 17:00 – 17:30 n Sonia Sharma Life & Medical Sciences (LIMES) Institute, University of Bonn Division of Cellular Biology, La Jolla Institute for Allergy & Environmental regulation of immune responses Immunology, Division of Cellular Biology, RNAi Center through the AhR/AhRR sensory system A systematic dissection of type I Interferon signaling using a high-throughput functional genomics approach 13:45 – 14:15 n Claudia Jakubzick 19:30 Speaker’s dinner Dept. of Pediatrics, National Jewish Health and Dept. of Immunology and Microbiology, University of Colorado Double-edged sword: Self-acquiring Batf3-dendritic cells Round table discussion 10:00 are required for anti-tumor immunity and graft rejection Gender Equality and Science 14:15 – 14:45 n Muzlifah Haniffa Moderation: Irmgard Mausz, LMU Center for Leadership and People Management Institute of Cellular Medicine, Newcastle University Functional heterogeneity of human mononuclear Even though conditions for women working in science have greatly improved, many female scientists are still deterred from pursuing a career in science at the highest levels. In the round phagocytes in health and inflammation table discussion the speakers will discuss about gender equality and careers in science and share their own experiences. 14:45 – 15:15 n Lisa Horvath Chair of Research and Science Management,Technical University Munich Attracting and retaining women in science Session 1 Welcome adress: Anne Krug, Barbara Conradt 13:00 15:30 – 16:00 Coffee Break Room D 0.30 4 5 Program SFB 1054 Session 1 CD103+ DCs require ligation of TLR3 for this purpose. This selectivity does not extend to antigen cross-presentation for T-cell proliferation but is required for induction of cytotoxicity. Thus, demonstrating the ability of DCs to induce functional CTLs is specific to the nature n Irmgard Förster, University of Bonn, Germany 13:15 of the pathogen-associated molecular pattern (PAMP) encountered by endogenous DC. Environmental regulation of immune responses Part 2: In transplantation, a major obstacle for graft acceptance in major histocompatibility through the AhR/AhRR sensory system complex (MHC) matched individuals is the mismatch of minor histocompatibility antigens. Minor H antigens are peptides derived from polymorphic proteins that can be presented by The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which senses antigen-presenting cells (APC) on MHC molecules. The APC subtype uniquely responsible environmental chemicals. Besides its important role in xenobiotic metabolism, the AhR has for the rejection of minor antigen-mismatched grafts had not yet been identified. Using three been identified as a potent immune regulator. AhR activity is regulated by feedback inhibition graft rejection models, we demonstrated that Batf3-dependent DCs are the APCs required through the AhR Repressor (AhRR). Using AhRR-EGFP reporter mice we could show, that for rejection of cells and grafts expressing mismatched minor antigens. The implication of the AhRR is mainly expressed in immune cells of the intestine and skin in response to AhR our findings for clinical transplantation is significant, as minor antigen reactivity is strongly stimulation. AhRR-deficient mice are protected from LPS-induced septic shock, producing implicated in the pathogenesis of multiple allograft tissues. The ability to specifically target strongly reduced levels of proinflammatory cytokines. In contrast, AhRR deficiency imposes minor antigen reactivity in transplant recipients has the potential to dramatically improve enhanced sensitivity to dextran sulfate induced colitis similar to that seen in AhR-deficient transplant outcomes. mice. We propose that constant stimulation of the AhR/AhRR pathway in response to dietary, microbial and environmental factors is essential for an adequate balance of barrier immunity. n Muzlifah Haniffa, Newcastle University, UK 14:15 n Claudia Jakubzick, University of Colorado, USA 13:45 Functional heterogeneity of human mononuclear phagocytes in health and inflammation Double-edged sword: Self-acquiring Batf3-dendritic cells are required for anti-tumor immunity and graft rejection Dendritic cells (DCs), monocytes and macrophages are a heterogeneous population of mono- nuclear phagocytes that are involved in antigen processing and presentation to initiate and The first half of the talk will illustrate how TLR3 and TLR7 ligands selectively activate pulmonary regulate immune responses to pathogens, vaccines, tumour and tolerance to self. In addition dendritic cells (DCs) to induce a cytotoxic T cell response (CTL) and when the DC is correctly to their afferent sentinel function, DCs and macrophages are also critical as effectors and matched: tumor antigen + TLR adjuvant an efficacious anti-tumor response occurs, whereas the co ordinators of inflammation and homeostasis in peripheral tissues. Harnessing DCs and second part of the talk will highlight the detrimental contribution of Batf3-dependent DCs macrophages for therapy has major implications for a wide range of clinical applications. (CD103+ and CD8+ DCs) for minor-antigen mismatched grafts. There has been a paradigm shift in our understanding of the development and function of mononuclear phagocytes. Significant progress has been made in both human and mouse Part 1: DCs are required for the induction of CTL. In most tissues, including the lung, the mononuclear phagocyte biology. This progress has been accelerated by comparative biology resident DCs fall into two types expressing the integrin markers CD103 and CD11b. The current analysis between mouse and human, which has proved to be an exceptionally fruitful strategy supposition is that DC function is predetermined by lineage, designating the CD103+ DC as to harmonise findings across species. Such analyses have provided unexpected insights and the major cross-presenting DC able to induce CTL. We found that Poly I:C (TLR3 agonist) facilitated productive reciprocal and iterative processes to inform our understanding of human or R848 (TLR7 agonist) do not activate all endogenous DCs. CD11b+ DCs can orchestrate and mouse mononuclear phagocytes. In this seminar, I will discuss the strategies, power and a CTL response in vivo in the presence of a TLR7 agonist but not a TLR3 agonist, whereas utility of comparative biology approaches to integrate recent advances in human and mouse 6 7 Program SFB 1054 mononuclear phagocyte biology and its potential to drive forward clinical translation of this generation of anti-inflammatory Th17 cell functionalities with implications for cutaneous knowledge. I will also present a functional framework on the parallel organisation of human tolerance mechanisms. Our discovery of GM-CSF-only producing T helper cells further adds to and mouse mononuclear phagocyte networks. the growing complexity
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