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Environmental Immunology

PD Dr. Stefanie Gilles
Research Group Leader Environmental Immunology
Environmental 伟德国际_伟德国际1946$娱乐app游戏icine

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About our Research

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What makes an allergen an allergen? Which signals must be emitted by harmless foreign proteins, on air-borne pollen for example, in order to be mistakenly classified by the mammalian immune system as harmful and for allergic sensitization to set in? How does allergic sensitization work?

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Our work focuses on the interaction of airborne allergens, such as pollen, with the innate immune system of the respiratory tract, and on the dendritic cell-mediated T-cell response. Research on the house dust mite allergen has highlighted the importance of activating the innate immune response as a prerequisite for allergic sensitization. We are particularly interested in finding out if there is a specific signaling pattern mediated by innate immune system receptors that paves the way to allergic sensitization to pollen.

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Allergens and the Immune System

Much of our current work focuses on pollen. On the one hand, this is due to the fact that pollen is one of the most relevant allergy triggers in the outside air and allergic rhinitis is very common in industrialized countries. However, pollen is also an interesting model for looking for signals from the innate immune system that are activated by allergens – or how these differ between different allergens. Interestingly, most of the currently known major pollen allergens do not activate the innate immune system themselves. This is in contrast to the major house dust mite allergens, some of which directly activate pattern recognition receptors (PRRs), e.g. B. DC-SIGN, or act as co-ligands for such receptors, e.g. TLR4. Therefore, comparison between the immune responses to isolated pollen proteins as well as to pollen extracts and defined fractions thereof can help to identify receptors and downstream signaling pathways that initiate or promote allergic sensitization. In the past we have discovered pollen-associated lipid mediators that act as chemoattractants for a variety of innate immune cells, such as neutrophils and eosinophils, or that affect dendritic cell function and thus modulate DC-mediated T helper cell responses toward Th2. We later identified adenosine as an important immunomodulator in pollen extracts. In the mouse allergy model, adenosine from pollen had opposite effects during the different phases of the allergic immune reaction: on the one hand, a tolerogenic effect during the sensitization phase, on the other hand, in already sensitized (allergic) animals, a pro-inflammatory effect.

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Pollen and Virus

Another current focus of our research is the interaction between pollen and pathogens, especially viruses, on the mucous membrane of the respiratory tract. An important investigation model are nasal epithelial cells. We have developed a technique for rapid expansion of nasal epithelial cells from small tissue samples obtained from defined donors, such as those with allergies or healthy individuals. The cells are then differentiated into organoids ("air-liquid interface cultures"). Differentiated nasal epithelial cell cultures form a stable physical barrier composed of tight junctions and contain mucus-producing goblet cells and ciliated cells. We recently published that pollen exposure impairs the innate immune response to respiratory viruses, e.g. B. rhinoviruses (HRV) and respiratory syncytial viruses (RSV). It does this primarily by inhibiting the antiviral type I and type III interferon response. In addition, in a large-scale, international data analysis, we found indications that the pollen count in spring could also promote SARS-CoV-2 infections. We want to check this in cell culture experiments in the future and examine the mechanisms in detail.

Team

Annika Eggestein
Student (PhD)
Environmental 伟德国际_伟德国际1946$娱乐app游戏icine
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Swetlana Urban
Student (PhD)
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Caroline Holzmann
Student (Ph.D.)
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Daria Luschkova
Assistant Physician
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