3rd International Symposium on "Autoinflammation breaks Barriers"

Contribution List

36. An Extracorporeal Circulation Mouse Model for Simultaneous Measurements of Dynamic Contrast-Enhanced Arterial Input Functions and Radiotracer Blood Concentrations

Poster

In small animals quantification of the dynamic arterial input function (AIF) is equally challenging for PET and MRI. AIF measurements provide the basis for kinetic modeling of both MR contrast agents (CA) and PET tracers.

Methodology:
Intracranial tumor-bearing mice received an extracorporeal shunt from the femoral artery to the tail vein. MRI scanning was performed using a 9.4 T MRI (Bruker...

24. Analysis of regulation of S100A8/A9-expression in phagocytes via CRISPR/Cas9 genome editing

Poster

The alarmins S100A8 and S100A9 are important signaling molecules during the innate immune response of monocytes and neutrophils. Indeed, S100A8 and S100A9 are dys-regulated in numerous tumors and inflammatory diseases. To gain insights into mechanisms of transcriptional regulation of S100A8/A9, four candidate transcription factors were tested for their impact on S100A8/A9 expression in murine...

31. Are B cells attracted by T follicular helper cells in experimental central nervous system autoimmunity?

Poster

Maike Hartlehnert (1), David Schafflick (1), Tobias Lautwein (1), Jan-Kolja Strecker (1), Tanja Kuhlmann (2), Heinz Wiendl (1), Gerd Meyer zu Horste (1)
(1) Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany; (2) Institute of Neuropathology, University Hospital Münster, Münster, Germany.

T follicular helper (TFH) cells are a CD4+ T...

15. Characterization of pericytes during autoreactive immune cell invasion into the CNS

Poster

The blood-brain barrier (BBB) is a major regulator of the central nervous system (CNS) homeostasis. In numerous neurological disorders the impairment of the BBB leads to the entry of immune cells and molecules into the CNS causes neuronal dysfunction and degeneration. Although there is a growing interest in understanding the role of pericytes as component of the BBB, little is known about...

12. Cutaneous over-expression of RANKL leads to suppression of anti-microbial immune responses

Poster

Cutaneous infections are controlled by the skin immune system eliciting innate as well as adaptive anti-microbial immune responses. Different studies, including our work, revealed that critical involvement of the tumor necrosis factor (TNF)/TNF receptor superfamily are regulating the cutaneous immunity. However, to complete their life cycle, pathogenic microorganisms need to suppress host...

20. DAMP-induced proinflammatory mechanisms affect the alveolar epithelial barriers during acute lung injury (ALI)

Poster

Acute lung injury (ALI) is a heterogeneous lung injury characterised by infiltration of phagocytes in the lungs. Alveolar epithelial cells (AECs) are an essential part of the respiratory barrier in lungs for gas exchange and protection against pathogens. During ALI the alveolar capillary barrier, which is made of the epithelial layer and the endothelial layer, is disrupted. Endogenous Damage...

23. Detecting bacteria-induced infective endocarditis by elemental mass spectrometric imaging

Talk

Staphylococcus aureus-induced infective endocarditis (IE) is a life threatening disease. To investigate and characterize IE in vivo, we have recently established a mouse model [1], [2]. IE is induced by placing a permanent catheter into the right carotid artery to irritate the aortic valves and provide a seed for formation of bacterial vegetations. Pathology of IE accumulates different amounts...

22. Dietary supplementation with conjugated linoleic acid influences CNS autoimmunity via the gut-brain axis

Talk

Multiple sclerosis (MS) is a multifactorial disorder, thus genetic disposition but also environmental factors are known to influence disease susceptibility and activity. This environmental modulation of central nervous system (CNS) autoimmunity can, inter alia, be mediated by the gut-brain axis, which is affected by nutritional components. Previous studies describe an influence of the...

18. Dimethyl fumarate treatment impairs T cell metabolism in multiple sclerosis patients

Poster

Dimethyl fumerate (DMF) is an approved immune-modulatory drug for treatment of relapsing remitting multiple sclerosis (RRMS). Although DMF treatment leads to beneficial clinical effects, around 17% of patients develop a lymphopenia characterized by sustained decrease of lymphocyte counts within blood. In parallel, DMF-treated patients exhibited decreased frequencies of memory T cell (TM) while...

32. Discovery of a species-spanning family of bacteria-derived cell-penetrating effector proteins

Poster

Many pathogenic bacteria secreted effector proteins directly into the eukaryotic host cell cytoplasm through their type III secretion system (T3SS), where they exert a number of effects that enable the pathogen to survive and to escape the host defense mechanisms. Lately, we could identify the Yersinia effector YopM as well as Salmonella-derived SspH1 as the first bacteria-derived...

33. Evaluation of the endothelial permeability of breast tumors with an albumin-binding contrast medium

Poster

Purpose: To evaluate whether the change of endothelial permeability during tumor progression can be assessed with the albumin-binding contrast medium gadofosveset in MRI.

Material and Methods: For the MRI protocol, anatomical T2, diffusion-weighted, T1/T2 map and dynamic contrast-enhanced sequences after the administration of gadofosveset trisodium were acquired. For the longitudinal study,...

26. FRET-based MMP14 probes for the investigation of invadopodia of invasive cancer cells

Poster

Metastatic tumor cells breach the barriers posed by the basement membrane, the interstitial connective tissue and the blood vessel wall in the so-called metastatic cascade. For invasion, both adhesion to the extracellular matrix and a spatially matched proteolysis of the extracellular matrix are essential. Therefore, invasive cancer cells form actin-rich protrusions on which β1 integrins and...

21. Hypersecretion of S100A8/A9 in non-classical autoinflammatory diseases

Poster

Introduction: Hereditary autoinflammatory diseases (AID) are a group devastating disorders characterized by chronic inflammation and unprovoked activation of phagocytes. Classical AIDs are caused by mutations in the NLRP3-inflammasome, leading to excess of IL-1β-release, whereas inflammation in non-classical AID (ncAID), e. g. PAPA- (Pyogenic sterile Arthritis, Pyoderma gangrenosum, Acne)...

16. Mechanism and consequences of interactions between immune cells and endothelial cells at the blood-brain-barrier - implications for CNS inflammatory diseases

Poster

A common feature of inflammatory CNS diseases such as multiple sclerosis, rasmussen encephalitis, neuromyelitis optica or the Susac syndrome represents the transmigration of autoreactive T cells through the brain endothelial cell layer into the CNS, where they can cause tissue destruction and neuronal loss.
With this project we are aiming to investigate the molecular mechanisms of immune cell...

28. MRI investigation of clearance mechanisms of the Glymphatic System

Poster

Introduction:
The Glymphatic System has been identified as a metabolic waste products clearance system in the brain, depending on paravascular pathways and the flux of cerebrospinal fluid (CSF). CSF flow elutes soluble proteins and waste, and is intensified during sleep or anesthesia. In our experiments we evaluate the effect of brain state on distribution of contrast agent and water...

14. NLRP3 inflammasome activity in monocytes is regulated by 12/15-lipoxygenase.

Poster

Background: Activation of the NLRP3 inflammasome is a major inflammatory pathway in monocytes in response to various exogenous and endogenous stimuli. However, negative regulation of inflammasome activity is not well understood. Glucocorticoids (GC) are drugs of choice for the treatment of many inflammatory diseases. Recently, we could show that treatment of monocytes with GC leads to...

30. Pathogenic signature of Th17 cells enhances during long-term natalizumab treatment – potential implications for disease rebound?

Poster

A multiple sclerosis (MS) treatment is natalizumab (NAT; Tysabri®), a monoclonal antibody against the cell adhesion molecule very late antigen-4 (VLA-4), which prevents leukocytes to adhere to the blood-brain-barrier (BBB) and therefore invasion into the central nervous system (CNS). However, after NAT cessation, MS patients frequently experience a disease rebound, often exceeding pretreatment...

10. Relevance of neutrophil extracellular traps during vessel damage in skin-limited IgA immune complex vasculitis

Poster

Immune complex vasculitis is a vascular inflammation that mainly affects small blood vessels. Initial steps are formation of immune complexes in the vessel, followed by neutrophil and IC interaction, accumulation, deposition, activation and ensuing destruction of vessel wall. It is unknown how and which cytotoxic components cause the vessel damage. Stimulated neutrophils produce extracellular...

19. Role of fibronectin and serine proteases in S. aureus invasion into host cells

Poster

Staphylococcus aureus is not only an extracellular but also an intracellular pathogen. The host cell invasion of non-professional phagocytes essentially contributes to infection development. The fibronectin bridging between S. aureus FnBPs and alpha5beta1 integrins on the host cell side that facilitates the uptake of staphylococci is well investigated. In a recent in vitro study we showed...

11. The alarmin S100A8/S100A9 is a key regulator of monocyte activation and homing

Talk

Phagocytes are fast migrating cells throw-out the body and are important for the pathogen defense. Therefore these cells have to migrate and transmigrate to sites of infection in a coordinated way. The cellular dynamics underlying inflammatory activation of monocytes are regulated by signaling pathways that involve changes in intracellular calcium, GTPase activation and specific protein...

40. The phagocytic activity of macrophages derived from different origins

Poster

Macrophages, as professional phagocytic cells, remove apoptotic cells during inflammation but also in routine tissue homeostasis. Additional to their defining phagocytic function, macrophages within different tissues exhibit unique properties. The mechanisms which control this phenotypic and functional heterogeneity among macrophages are currently under investigation. We studied the phagocytic...

17. The role of S100A8 and S100A9 in murine keratinocytes

Poster

Introduction: S100A8 and S100A9, also known as myeloid-related protein-8 (MRP8) and MRP14, are damage-associated molecular pattern molecules (DAMPs). Both proteins are highly up-regulated in autoimmune diseases of human skin like psoriasis as well as in certain in vivo models (e.g. Imiquimod induced psoriasis like phenotype).
Methods: Keratinocytes collected from adult tail skin of either...

13. The Yersinia outer protein M (YopM) reduces keratinocyte hyperproliferation and neutrophil infiltration psoriasis-like inflammation in mice

Poster

Psoriasis is an inflammatory skin disease affecting around 2-4 % of the western European population. Patients suffer from red, itchy and scaly plaques and an impaired quality of life. Several treatment options are available, but with higher efficacy often toxicity and/or therapy costs are rising.
The Yersinia outer protein M (YopM) was the first bacterial effector protein discovered to be a...

27. Time-lapse MRI as dynamic single cell tracking imaging technique for diagnosis of inflammation

Poster

Introduction:
Time-lapse MRI enables imaging of slowly moving individual immune cells in the intact brain in vivo. Applying this method to naïve mice and mice suffering from experimental autoimmune encephalomyelitis (EAE) has previously shown altered immune cell dynamics. The aim of this study is to evaluate time-lapse MRI of the brain under non-CNS associated inflammatory...