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Otto Loewi Forschungszentrum
ResearchOtto Loewi Research CenterResearch centers and institutesMedical University of Graz

Research team Böhm

Research focus: The role of eosinophils in allergic and inflammatory diseases

PI: Eva Böhm

Focus: Our research unit is interested in dysregulated intracellular signaling pathways associated with chronic inflammatory processes with a main focus on eosinophilic disorders such as bronchial asthma and eosinophilic esophagitis.

Network: In vitro and in vivo studies on mechanisms of eosinophilic inflammation are performed by the research team at the Division of Pharmacology. Mutual collaborations exist with the research groups of Akos Heinemann (biology of lipid mediators), Rudolf Schicho (histology and fluorescence microscopy) and Gunther Marsche (lipid metabolism). Patient samples are provided in scientific collaboration by the Clinical Departments of Pulmonology and Gastroenterology. Close cooperation also exists with the Ludwig Boltzmann Institute for Pulmonary Vascular Research and international partners.

Projects

The molecular circadian clock in eosinophilic disorders

  • Asthma is characterized by a distinct circadian signature. This circadian rhythmicity is reflected in both nocturnal respiratory symptoms and increased eosinophil inflammation in the early morning hours. The mammalian central pacemaker is localized in the suprachiasmatic nucleus of the hypothalamus and coordinates subordinate, autonomous, molecular circadian clocks present in all organs and cells of the body. These molecular circadian clocks are a complex network of transcription-translation feedback loops comprising transcription factors and nuclear receptors such as BMAL1, CLOCK, PER, CRY, REV-ERB, and ROR. Disruption or disturbances of the molecular circadian clock increase the risk for numerous diseases such as psychiatric, metabolic and inflammatory disorders. In particular, the nuclear receptor and transcriptional repressor REV-ERB alpha is known to gate between the molecular circadian clock and the immune system. In this project we investigate the role of the molecular circadian clock in asthmatic patients, patients with eosinophilic esophagitis and respective experimental models. The aim is to determine whether the components of the molecular circadian clock can be used as prognostic markers or as therapeutic targets for pharmacological intervention.
  • Duration: 2020-2024
  • Funded by: FWF, Medical University of Graz (DOC 129, RespImmun)
  • Project partners: Leigh Marsh (Ludwig Boltzmann Institute for Pulmonary Vascular Research, Graz); Akos Heinemann (Division of Pharmacology, MUG); Eva Gruden/Rudolf Schicho (Division of Pharmacology, MUG), Robert Gurke (University of Frankfurt), Hannah Durrington (University of Manchester), Elizabeth Jacobsen (Mayo Clinic Scottsdale).

The IL-23/Th17 axis in chronic respiratory diseases

  • Although glucocorticoids are the gold standard of anti-inflammatory therapy in asthma and COPD, there are still steroid-resistant patients with poor treatment response. Interleukin-23 (IL-23), activated Th17 lymphocytes and neutrophil granulocytes seem to play a crucial role in the development of steroid resistance. IL-23-induced JAK/STAT signaling mediates the expression and synthesis of other cytokines such as IL-17A, IL-17F, IL-21 and IL-22. IL-17 in turn stimulates the release of G-CSF, IL-8 and IL-6 and thus promotes the development of neutrophilic inflammation. In this project we investigate the activation of the IL-23/Th17 axis and the JAK-STAT pathway in patients with refractory forms of bronchial asthma and COPD, and aim to evaluate the therapeutic potential of JAK inhibitors to break steroid resistance.
  • Duration: 2021-2025
  • Funded by: FWF, Medical University of Graz (DOC 129, RespImmun)
  • Project partners: Philipp Douschan (Pulmonology, Med Uni Graz), Peter Valentin Tomazic (ENT, Med Uni Graz)

Division of Pharmacology

Assoz.-Prof.in Priv.-Doz.in Mag.a Dr.in
Eva Böhm 
T: +43 316 385 74103
E: eva.sturm@medunigraz.at
Eva Sturm
Research profile

Team

Members

Forschungsteam Böhm

Research gallery

The molecular circadian clock (left). The molecular circadian clock regulates the daytime-dependent recruitment of eosinophils into the lungs (right), leading to increased inflammation and severe symptoms especially in the early morning.
Figure 1
The molecular circadian clock (left). The molecular circadian clock regulates the daytime-dependent recruitment of eosinophils into the lungs (right), leading to increased inflammation and severe symptoms especially in the early morning.
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The IL-23/Th17 pathway in chronic airway inflammation. IL-23-induced JAK/STAT signaling mediates the expression and synthesis of other cytokines from polarized Th17 cells. IL-17 in turn stimulates the release of G-CSF, IL-8 and IL-6 and thus promotes the development of neutrophilic inflammation. Blocking the IL-23/TH17 axis might be a therapeutic option to treat neutrophilic lung inflammation.
Figure 2
The IL-23/Th17 pathway in chronic airway inflammation. IL-23-induced JAK/STAT signaling mediates the expression and synthesis of other cytokines from polarized Th17 cells. IL-17 in turn stimulates the release of G-CSF, IL-8 and IL-6 and thus promotes the development of neutrophilic inflammation. Blocking the IL-23/TH17 axis might be a therapeutic option to treat neutrophilic lung inflammation.
Image size: 1000 x 680
File size: 191 KB
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