Lecture Series on Chronic Inflammation

Weekly, every Thursday

• Are you familiar with chronic inflammatory diseases?
• Have you heard that any organ can be affected?
• Joints, skin, kidneys, nerves, intestines – all?
• understand one inflammatory disease – cure them all?

…. these and further topics will be covered in the new Lecture Series given by our Postdoc Fellows.

when: 14:00-15:00, starting 18.10.2018
where: DRFZ, Seminar room 3, Charitéplatz 1
visitors: Virchowweg 12

25.10.2018 - Daniel Schulz

The role of stromal niches in chronic inflammation

It has recently been acknowledged that a variety of immune cells that cause long-term inflammation depend not only on inflammatory mediators
and antigen but also on survival factors that are thought to be secreted by tissue-resident stromal cells. In these niches, cells proved to be
refractory to conventional therapies, hence an important therapeutical question emerged what separates a benign from a malign niche.

Reviews from stroma lecture

Cusick, M. F., Libbey, J. E., & Fujinami, R. S. (2012). Molecular mimicry as a mechanism of autoimmune disease. Clinical Reviews in Allergy and Immunology, 42(1), 102–111. http://doi.org/10.1007/s12016-011-8294-7

Smart, B. A. (2008). Duration of Humoral Immunity to Common Viral and Vaccine Antigens. Pediatrics, 122(Supplement 4), S228.1-S228. http://doi.org/10.1542/peds.2008-2139LLLL

Bernardo, M. E., & Fibbe, W. E. (2013). Mesenchymal stromal cells: Sensors and switchers of inflammation. Cell Stem Cell, 13(4), 392–402. http://doi.org/10.1016/j.stem.2013.09.006

Mikkola, H. K. A. (2006). The journey of developing hematopoietic stem cells. Development, 133(19), 3733–3744. http://doi.org/10.1242/dev.02568

Buckley, C. D., Barone, F., Nayar, S., Bénézech, C., & Caamaño, J. (2015). Stromal Cells in Chronic Inflammation and Tertiary Lymphoid Organ Formation. Annual Review of Immunology, 33(1), 715–745. http://doi.org/10.1146/annurev-immunol-032713-120252

Barone, F., Nayar, S., Campos, J., Cloake, T., Withers, D. R., Toellner, K.-M., … Buckley, C. D. (2015). IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs. Proceedings of the National Academy of Sciences, 112(35), 11024–11029. http://doi.org/10.1073/pnas.1503315112

Hand, T. W., Vujkovic-Cvijin, I., Ridaura, V. K., & Belkaid, Y. (2016). Linking the Microbiota, Chronic Disease, and the Immune System. Trends in Endocrinology and Metabolism: TEM, 27(12), 831–843. http://doi.org/10.1016/j.tem.2016.08.003

01.11.2018 - Randy Lindquist

Imaging of inflammation

Inflammation, since it was defined two millenia ago, is primarily a characteristic of tissues. Even when systematic inflammation occurs, it manifests
very differently in various tissues, depending on the tissue’s physiological role. For example, resident memory T cells perform immunosurveillance
in the peripheral tissues where pathogens enter the body, while germinal center reactions occur in secondary lymphoid organs and ectopic tertiary
lymphoid tissue. The physiology of immune cells and pathogens is influenced by many parameters, including oxygen tension, temperature, perfusion,
secreted factors derived from cells or microbial flora, and contacts with other cells and extracellular matrix. As the influence of these parameters on
cellular function is different for each cell type involved in immune responses, we argue that a comprehensive analysis can only be performed in
intact, living tissue. This requires specialized imaging techniques, the uses of which both clinically and in basic research will be discussed.

08.11.2018 - Gitta Heinz

RNA-based gene regulation in chronic inflammation

This lecture will give an overview on gene regulatory mechanisms that play an important role in establishing and maintaining chronic inflammation
and that are driven by RNA molecules. These are on the one hand miRNAs, which modulate gene expression by directly binding to their target
mRNAs and promoting translational repression or degradation. Other non-coding RNAs were also described to be involved in inflammatory
processes, even though their molecular functions are not fully understood. On the other hand the translation and stability of mRNA molecules, particularly cytokine mRNAs, is tightly regulated via sequence elements within the 3’ untranslated region. As an outlook, novel diagnostic and therapeutic approaches that make use of the above-mentioned mechanisms will be discussed.

List of reviews

Alexander M and O‘Connell RM, Noncoding RNAs and chronic inflammation: Micro-managing the fire within. Bioessays. 2015 Sep;37(9):1005-15
https://doi.org/10.1002/bies.201500054

Chew CL at al., Noncoding RNAs: Master Regulators of Inflammatory Signaling. Trends Mol Med. 2018 Jan;24(1):66-84
https://doi.org/10.1016/j.molmed.2017.11.003

Schwerk J and Savan R, Translating the Untranslated Region. J Immunol. 2015 Oct 1;195(7):2963-71
https://doi.org/10.4049/jimmunol.1500756

15.11.2018 - Laleh Khodadadi

The maintenance of memory plasma cells

What derives a plasma cell to become memory? Is it an intrinsic competence or extrinsic stimulation or combination? Which internal signals are involved in this process? What are external supporters? What are survival factors in inflammation and autoreactive disease? More information about maintenance of protective ad autoreactive memory cells will help scientists in one hand, to design more effective vaccines inducing life-long protection against infectious diseases, in the other hand, to target efficiently autoreactive memory plasma cells. I will discuss about the internal and external factors in maintenance of memory plasma cells.

22.11.2018 - Axel Schulz

High-Parametric Mass Cytometry: A single-cell, system-level technology for deciphering chronic inflammatory diseases

Mass cytometry permits deep cellular phenotyping in clinical immunology and basic research, with more than 40 parameters that can be measured
simultaneously at single-cell level in one assay. This is achieved by combining principles of flow cytometry and inductively coupled plasma mass
spectrometry (ICP-MS), a technology that has been developed for trace metal analysis.
This lecture introduces the principles of mass cytometry and its potential applications in the context of immunology research. We will explore how
questions in chronic inflammation can be addressed by mass cytometric assays and will discuss an example of a system-level analysis of
peripheral blood immune cells in patients with rheumatoid arthritis.

29.11.2018 - Yvette Meißner

Inflammation, rheumatoid arthritis and cardiovascular disease

Some of the pivotal pro-inflammatory mediators, including the cytokines tumor necrosis factor alpha (TNFα), interleukin 1 (IL-1) and interleukin 6
(IL-6), as well as the acute-phase reactant C-reactive protein (CRP), are involved in atherogenesis and eventually in the development of coronary
artery diseases. The autoimmune disease of rheumatoid arthritis is characterized by chronic inflammation primarily affecting the joints. However,
patients with rheumatoid arthritis have an increased burden of cardiovascular morbidity and mortality compared to the general population. This
lecture will summarize current insights into chronic inflammation as a link between cardiovascular events and rheumatoid arthritis. Furthermore,
experiences from the German observational cohort RABBIT (Rheumatoid Arthritis: Observation of Biologic Therapy) with regard to cardiovascular
diseases will be presented.

06.12.2018 - Asylkhan Rakhymzhan

Optical methods

Modern optical methods represent essential tools that are widely used to study complex processes in biology. Progress in technology increased
the level of research functionality allowing to perform experiments and address scientific questions that were not possible before. This lecture will
give an overview to the principles of different advanced optical techniques, such as multiphoton microscopy, super-resolution methods, optical
coherence tomography, fluorescence life-time imaging. We will discuss the application of these techniques to study the pathology of chronic
inflammation in different organs.

13.12.2018 - Randy Lindquist

Chronic inflammation and cancer

Virchow noticed this association 150 years ago, that many sites of chronic inflammation are associated with the subsequent development of cancer.
Genetic evidence has clarified the mechanisms by which this occurs, how chronic inflammatory signaling can induce the development of certain
lymphoid and non-lymphoid malignancies, and how inhibition of inflammation can prevent this. Recently, the development of immune-modulating
drugs to induce anti-tumor T cell responses has shown the converse of this, how tumors use chronic exposure to antigen to desensitize T cells and
prevent adaptive immune responses to tumor neoantigens. Better understanding of the mechanisms by which peripheral tolerance is maintained,
and how this is manipulated by cancers, can lead to improved therapies.

20.12.2018 - Shintaro Hoyjo

Helper T cells in chronic inflammation

Differentiation of resting memory T helper (Th) cells occurs independently of that of effector follicular T helper (Tfh) cells

IL-2 signaling is crucial for the differentiation of resting memory Th cells

B cells control the bifurcated differentiation programs for effector and resting memory Th cell lineages

10.01.2019 - Stefan Frischbutter

Drug Discovery in academia

More than one hundred years ago Paul Ehrlich developed chemotherapy and thereby pioneered drug discovery. Since then, this research area has
turned into a multi-billion-dollar business which was for a long time dominated by the pharma industry. However, this is about to change: drug
discovery in academic institutions becomes more and more popular again. Based on my own experience and using several examples I will
highlight the value of academic drug discovery for the development of sophisticated therapeutic approaches especially for indications with unmet
medical need.

17.01.2019 - Patrick Maschmeyer

Functions of microRNAs in chronic inflammatory diseases

MicroRNAs (miRNAs) are small (~ 22 nucleotide long), single-stranded non-coding RNAs. They are important regulators of gene expression in
cells and are critical in a multitude of cellular processes such as cell division, cell survival or migration. Recent studies demonstrated that miRNAs
can contribute to the pathogenesis of chronic inflammatory diseases. This lecture will highlight the relationship between miRNAs and chronic
inflammatory conditions and focus on mechanistic functions of miRNAs in the pathology of chronic inflammation.

24.01.2019 - Marina Babic - Cac

Immune checkpoints as therapeutic targets in inflammation

Immune response is a result of a very delicate balance between activating and inhibitory signals provided by the molecules expressed on the surface
of immune cells.
While too little inflammation results in the increased susceptibility to pathogens and possible outgrowth of malignant cells, the consequence of too
much inflammation is autoimmunity and immune pathology.
In the recent decade, cancer therapy was revolutionized by the development of drugs targeting immune checkpoints, receptors such as CTLA-4 and
PD-1, thus interrupting the inhibitory signal and unleashing the T cell mediated anti-tumor response.
This lecture will give an overview on the current progress in targeting T cell checkpoints, both co-stimulatory and inhibitory receptors, as well as how
the experience from treating cancer with checkpoint blockade could be used as a therapeutic approach in autoimmune rheumatic diseases.

Geschäftsstelle Leibniz WissenschaftsCampus Chronische Entzündung Mag. Dr. Elke Luger Tel +49-(0)30-28460-737 luger@drfz.de Zur Person