Lung Immunology

Our mission is to elucidate the processes and mechanisms underlying the progression and chronification of allergic airway inflammation and, thus, the formation of different asthma endotypes in order to identify novel targets for customized therapeutic intervention.

Bronchial asthma is one of the most common chronic diseases in the world and developed to a major health problem of the western world by reason of very high and still increasing incidence and prevalence recorded over the last decades. According to the WHO-funded GINA (Global Initiative for Asthma) Report on the Global Burden of Asthma as many as 300 Million people of all ages and all ethnic backgrounds suffer from asthma with incidences exceeding 10-19% of the population in the US, the UK and Australia.

The disease is clinically characterized by a variable degree of broncho-obstruction together with cough, chest tightness, shortness of breath, and wheezing, which are caused by the development of airway hyperresponsiveness (AHR), structural remodeling of the airway wall and mucus hypersecretion. Depending on the severity of the disease the degree of each of these hallmarks, especially impaired lung function, displays high variability actually leading to the definition of several different asthma endotypes. It is likely that these endotypes arise from a different etiology and pathogensis, which necessitates a customized therapy in thes sense of precision medicine. This can only be established on the basis of an deep understanding of those pathogentic mecahnisms that ultimately lead to the formation of each disease endotype. Nevertheless, the complex phenotype of bronchial asthma arises from chronic inflammation of the airways in response to the inhaled allergen(s).

In mild-to-moderate asthma this inflammation represents a classic allergic immune response whereat T helper 2 (TH2) cells play a critical role in directing the allergic immune response. By producing a characteristic pattern of cytokines, chemokines and growth factors these cells drive allergic inflammation that follows allergen inhalation, while eosinophils act as the main effector cell type of the allergic inflammatory response. Eosinophil products such as cytotoxic proteins and enzymes are involved in the development of AHR and cause marked destruction of the airway tissue, which in turn triggers repair processes. In contrast, the inflammatory response underlying the formation of severe asthma appears to be much more complex and involves prominent infiltration of several leukocyte subsets (e.g. NK cells) producing the highly proinflammatory cytokine Interleukin 17 (IL-17).

The mechanisms underlying the aggravation of mild-to-moderate asthma towards the development of a severe phenotype still remain enigmatic. Acute episodes of asthma aggravation – so-called exacerbations – represent a typical hallmark of asthmatic diseases and are typically triggered by viral or bacterial infection of the airways. Such infections lead to an amplified inflammatory reaction resulting in a further increase in mucus production and a further decline in lung function. Interestingly, also in acute asthma exacerbation neutrophils and IL-17-producing leukocyte subsets infiltrate into the airways, which at least in parts resembles the inflammatory situation in severe asthma. To date it is not clear, which factors orchestrate the differentiation and the recruitment of these cells to the lung and what is actually their role in the pathogenesis of acute asthma exacerbations.

Eventually, another regulatory level could be the key for understanding this process, namely the balance between generally pro- and anti-inflammatory mediators. Clinical studies clearly demonstrate that pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), IL-1β and IL-6 as well as growth factors like granulocyte-macrophage colony stimulating factor (GM-CSF), neurotrophins or vascular-endothelial growth factor (VEGF) are produced in large amounts in airways of asthmatic patients, whereas the production of anti-inflammatory mediators such as IL-10 or relatively new members of the IL-1 cytokine family such as IL-37 are markedly decreased. These mediators cannot be attributed to the formation of a special immune response, but generally amplify all kinds of inflammation by activating the transcription factor nuclear factor κB (NFκB). This in turn seems to result in a predominance of pro-inflammatory factors permanently overwhelming counterbalancing feedback loops, and loss of control of inflammatory processes (and the resulting symptoms). This ultimately leads to creating an environment allowing chronic inflammation of the airways. Actually, recorvery of this control represents the aim of every current asthma therapy.

This research group focuses on understanding these regulatory levels in order to find novel targets for therapeutic intervention. Thereby, the development and use of appropriate models reflecting different asthmatic phenotypes is a major part of the research strategy. Actual research projects are:

• Viral induced acute exacerbations of allergic bronchial asthma
• The role of IL-17 producing NK cells in acute aggravation of allergic asthma
• The effects of the α-melanocyte stimulating hormone (α-MSH) and its receptor system in the immune-pathogenesis of allergic asthma
• The function and mode of action of IL-37 during asthma pathogenesis

BMBF
Member of Deutsches Zentrum für Lungenforschung (DZL), Research Center North (ARCN); Disease Area Asthma/Allergy:

• LI-JRG-1: JRG Asthma Mouse Models (PI: M. Wegmann)
• DA-AA-TFP: Translational Flagship Project (Coordinator: M. Wegmann)
• Verbundprojekt: POC-Sensorplattform für chronisch-entzündliche Atemwegserkrankungen (EXASENS) –
  Teilvorhaben: Vor-Ort-basierte Exazerbationsdiagnostik bei Asthma & COPD (FKZ: 13N13857)

LCI

• Leibniz Graduate School "Model Systems for Infectious Diseases", 2015-2018
• "Immuno-Pathogenesis of Influenza-Induced Asthma Exacerbation"; (Wegmann FZB / Gabriel HPI)

Begabten-Stipendium des Avicenna-Studienwerks (2022-24)

Mouse models of allergic bronchial asthma with its different phenotypes and disease stages are the methodological basis of our research. Currently, models reflecting acute, sub-chronic and chronic allergic asthma phenotypes are available.

Furthermore, we have established mouse models of virus-induced, acute exacerbation of allergic asthma as well as neutrophil asthma. Genetically modified mouse strains (knock-out, transgene, etc.) and different biological (antibodies, siRNA, DNAzymdes, etc.) are applied in order to perform mechanistic studies. Thus, we use a variety of methods to characterize the inflammatory reaction and immune response underlying asthma and its effects on lung structure and physiology. Since the analysis of lung function represents the benchmark criteria for clinical diagnostics as well as for the development and success of new therapeuticals, we put considerable emphasis on this method:

2022: Begabten-Stipendium - Abdulkadir Kalender

2018: Mainzer Abstract-Preis der DGAKI, Mainzer Allergie Workshop – Alexandra Schröder

2018: Golden Ticket Award, DZL Academy – Rebecca Bodenstein-Sgró

2017: ERS Short-Term Fellowship – Alexandra Schröder

2016: Bestes Poster des diesjährigen DZL-Jahrestreffens - Alexandra Schröder

2015: Bester Vortrag der DGP Herbstagung, Lübeck - Alexandra Schröder

2015: 1. Platz Best Abstract Award der DGP Jahrestagung, Berlin - Lars Lunding

2014: Doktorandenpreis der Deutschen Lungenstiftung - Lars Lunding
2014 Bester Vortrag der DGP Herbstagung, Lübeck - Lars Lunding
2014 Posterpreis der DGP Jahrestagung, Bremen - Lars Lunding

2013: Best Abstract Presentation Award, EAACI Annual Congress, Milano, Italy - Michael Wegmann
2013: Doktorandenpreis des Kreises Segeberg - Lars Lunding
2013: Posterpreis des NDI, Borstel - Lars Lunding
2013: Miltenyi autoMACS pro Award - Lars Lunding

2012: Posterpreis des wissenschaftlichen Beirats des FZB - Lars Lunding

2010: Promotionsstipendium des Exzellenzclusters „Inflammation at Interfaces“ – Lars Lunding

Head

PD Dr. Michael Wegmann

+49 4537 / 188-5830

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Scientific staff

Abdulkadir Kalender

+49 4537 / 188-5842

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Dr. Lars Lunding

+49 4537 / 188-5842

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Dr. Katrin Ramaker

+49 4537 / 188-6190

+49 4537 / 188-6930

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Technical staff

Franziska Beyersdorf

+49 4537 / 188-7680

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Linda Lang

+49 4537 / 188-7680

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