Next Graduation within the IRTG
Julia Kilian, IRTG fellow from April 2015 - March 2016, defended her dissertation on "The influence of circadian rhythms on the development of experimental allergic asthma" successfully on June 07th, 2022.
Congratulations!!!
New publication describes how the C5a/C5a receptor 1 axis controls tissue neovascularization
Platelets contribute to the regulation of tissue neovascularization, although the specific
factors underlying this function are unknown. Here, we identified the complement anaphylatoxin
C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory
mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an
inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation.
Growth factor- and hypoxia-driven vascularization was markedly increased in
C5ar1−/− mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with
increased collateralization, capillarization and improved pericyte coverage. Mechanistically,
we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4)
from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the
C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo.
In conclusion, we identified a mechanism for the control of tissue neovascularization through
C5a/C5aR1 axis activation in platelets and subsequent induction of the antiangiogenic
factor CXCL4.
The complement system – stepping out of the shadows and into the spotlight
The complement system has evolved during the past 1.2 billion years, making it one of the oldest parts of the immune system. Since its discovery around 100 years ago, the system has been mainly associated with its role as a first line defense system and guardian of the vascular space. However, several findings published during the past few years suggest that this might be only a small facet of the multiple functions of the system and that we have explored at best the tip of the iceberg.
Recent reports rediscovered complement production within cells, now with a fresh look on activation of complement factors within cells demonstrating novel roles for complement in cell homeostasis, survival and differentiation. The well know mechanisms of canonical pathway activation in response to C1q, MBL or Ficolin sensing, followed by C3 and C5 cleavage through C3 and C5 convertases have been complemented by non-canonical mechanisms, leading to cleavage and activation of complement factors in the circulation and within immune cells. Moreover, it has been shown that the complement system exerts multiple and bidirectional interactions with other sensor and effector systems of innate immunity thereby regulating and controlling responses of both, innate and adaptive immunity. With this plethora of novel functions, playing critical roles in acute and chronic inflammatory diseases, several molecules of the system became attractive therapeutic targets, eventually getting into the spotlight of the pharmaceutical industry.
The July themed issue of the British Journal of Pharmacology highlights in 10 articles recent discoveries that add to the extended view of the complement system with a fresh look on the functions of intracellular complement, thrombosis, trauma, hypertonia, kidney disease and COVID-19.
New Review summarizing IL-27-mediated mechanisms affecting protection and immunopathology in TB and possible therapeutic applications
In tuberculosis (TB), protective inflammatory immune responses and the pathological sequelae of chronic inflammation significantly depend on a timely balance of cytokine expression. In contrast to other anti-inflammatory cytokines, interleukin (IL)-27 has fundamental effects in experimental Mycobacterium tuberculosis (Mtb) infection: the absence of IL-27-mediated signalling promotes a better control of mycobacterial growth on the one hand side but also leads to a chronic hyperinflammation and immunopathology later during infection. Hence, in the context of novel host-directed therapeutic approaches and vaccination strategies for the management of TB, the timely restricted blockade of IL-27 signalling may represent an advanced treatment option. In contrast, administration of IL-27 itself may allow to treat the immunopathological consequences of chronic TB. In both cases, a better knowledge of the cell typespecific and kinetic effects of IL-27 after Mtb infection is essential. This review summarizes IL-27-mediated mechanisms affecting protection and immunopathology in TB and discusses possible therapeutic applications. The publication is available here.
Jörg Köhl ranked among the top 50 Immunology researchers in Germany
The academic research portal research.com presented its 2022 edition of top-ranked scientific-researchers from around the world in the field of Immunology. More than 6,300 scientist profiles have been examined with several indicators and metrics reviewed in order to consider each scientist’s inclusion in the ranking. In order to be considered for the ranking, the h-index threshold was set to 40 if most of the publications were in the field of immunology. The h-index was invented by J.E. Hirsch and is often used as a measure of a researcher's scientific quality and impact. Further, profiles and data from the scientific search engines Google Scholar and Microsoft Academic Graph were evaluated.
The aim of this ranking is to increase the visibility and transparency of the influential and innovative contributions of researchers around the world.
Jörg Köhl, Professor and Director of the Institute for Systemic Inflammation Research at the University of Lübeck was ranked #45 in Germany (out of 240 Professors from 35 German universities) with an h-factor of 74, >18,000 citations and 190 publications. Further, he ranked #887 in the world. The University of Lübeck was ranked #11 among all German universities in the field of Immunology.
Top Immunology Scientists – German Ranking
https://research.com/scientists-rankings/immunology/de
https://research.com/u/jorg-kohl
Top Immunology Universities – German Ranking
https://research.com/university-rankings/immunology/de
"Meine Promotion in 100 Sekunden"
Fabian Mey talks about doing a PhD at the University of Luebeck (and within the IRTG)!
Graduation 2019
07/2019 - Filipa Varela
Congrats!
Graduation 2019
08/2019 - Konstantina Antoniou
Congrats!
Graduation 2019
10/2019 - Dorinja Zapf
Congrats!
New Review Article Discussing Complement-Targeted Immunotherapy to Fight COVID-19 Infection
The COVID-19 pandemic keeps the world in suspense uniting clinicians and basic researchers in their efforts to better understand disease pathogenesis and develop effective clinical interventions. The complement system is an ancient part of innate immunity sensing highly pathogenic coronaviruses by Mannan-binding lectin resulting in lectin pathway activation and subsequent generation of the anaphylatoxins (AT) C3a and C5a as important effector molecules. Complement deposition in endothelial cells and high blood C5a serum levels have been reported in COVID-19 patients with severe illness, suggesting vigorous complement activation leading to systemic thrombotic microangiopathy (TMA). Strikingly, SARS-CoV-2 infected African Americans suffer from high mortality. Complement regulator gene variants prevalent in African Americans have been associated with a higher risk for severe TMA and multi-organ injury. These findings allow to apply knowledge from other complement-mediated diseases with TMA to better understand the mechanism underlying severe disease progression in COVID-19 infection.
Graduation 2019
10/2019 - Fabian Mey
Congrats!
New Publication online!
Research in the past decade revealed a large and hitherto not appreciated phenotypic heterogeneity of neutrophil granulocytes. Especially the tumor-associated N1 and N2 neutrophils that represent immunostimulatory and immunosuppressive subpopulations, respectively, have been subject of intensive research. As most knowledge regarding N1 and N2 neutrophils is derived from murine cancer models, we aimed to develop a model for the phenotypic polarization of human neutrophils in vitro. By providing an activating environment in form of a N1 polarization cocktail or mimicking the tumor environment in form of a N2 polarization cocktail, we were able to drive the polarization of primary human neutrophils in the cell culture toward N1-like and N2-like phenotypes, respectively. Furthermore, we applied our in vitropolarization model to investigate the hypothesis that intracellular pathogens polarize neutrophils toward an immunosuppressive phenotype with limited antimicrobial functions. Indeed, our findings indicate that N2-polarized neutrophils exert a markedly decreased capacity to kill the intracellular parasite Leishmania donovaniand, therefore, promote parasite persistence. Taken together our in vitropolarization model represents a step towards establishing an in vitroprotocol for the in-depthanalysis of N1 and N2 neutrophil subsets.
New article dealing with the role of C3/C3a in tissue priming of fibroblasts in arthritis
Arthritis typically involves recurrence and progressive worsening at specific predilection sites, but the checkpoints between remission and persistence remain unknown. Here,we defined themolecular and cellular mechanisms of this inflammation-mediated tissue priming. Re-exposure to inflammatory stimuli caused aggravated arthritis in rodent models. Tissue priming developed locally and independently of adaptive immunity. Repeatedly stimulated primed synovial fibroblasts (SFs) exhibited enhanced metabolic activity inducing functional changes with intensifiedmigration, invasiveness and osteoclastogenesis.Meanwhile, human SF frompatients with established arthritis displayed a similar primed phenotype. Transcriptomic and epigenomic analyses as well as genetic and pharmacological targeting demonstrated that inflammatory tissue priming relies on intracellular complement C3- and C3a receptor-activation and downstream mammalian target of rapamycin- and hypoxia-inducible factor 1a-mediatedmetabolic SF invigoration that prevents activation-induced senescence, enhances NLRP3 inflammasome activity, and in consequence sensitizes tissue for inflammation. Our study suggests possibilities for therapeutic intervention abrogating tissue priming without immunosuppression.
Welcome to the international Research Training Group 1911
"Immune regulation of inflammation in allergy and infection"
The interface between innate and adaptive immunity plays an important role for the initiation, perpetuation and resolution of chronic infections and allergic diseases. Accordingly, novel humoral and cellular signaling pathways have been identified in the research program in the context of allergic and infectious disease-related inflammation in vivo in defined disease models and at the molecular level. In the future will also consider environmental factors that can regulate the immune response towards allergens and pathogens through modulation of the microbiome composition. The doctoral researchers will clearly benefit from the broad spectrum of in vitro systems and in vivo models of inflammatory diseases offered by the IRTG and the expertise of the IRTG researchers within the fields of allergy and infection research. To better understand the similarities and the differences of the complex immunological networks underlying allergic and infection-associated inflammation, systems immunology approaches will be implemented that have been developed by our partner university in Cincinnati. With this program the IRTG aims at identifying novel target molecules or signaling pathways in order to come up with innovative therapeutic strategies and at educating immunologists for the domestic and international job market at the interface between allergy and infectious disease research.
The research program is supplemented by a structured qualification and cross-border supervisory concept with defined training modules that integrates student exchanges between the German and the US partner institutions. The qualification concept comprises an IRTG- specific seminar that integrates visiting researchers, jointly held courses, a yearly retreat, an international symposium and individualized educational as well as mentoring programs. General key skills will be imparted through the multiple course offers of the Graduate School Lübeck.
More information:
Research Area A "Environmental changes as culprits of maladaptive immune deviation in allergy"
Research Area B "Cellular cross-talk and molecular mechanisms controlling infections with intracellular pathogens"
News
Immunology Day on April 29th: Should I or shouldn't I? - Information about Corona and the vaccination
New Article dealing with the role of C3/C3a in tissue priming of fibroblasts in arthritis
New Review Article Discussing Complement-Targeted Immunotherapy to Fight COVID-19 Infection!
IRTG1911 Retreat 2020 as Virtual Retreat - October 15-16!
iRTG1911 - Immune Regulation of Inflammation in Allergy and Infection
University of Lübeck
Spokesperson: Prof. Dr. med. Jörg Köhl
