Research
Type 2 immune responses
The so-called type 2 immune response is a polarized response typically found during helminth infections, allergies and asthma. However, cells associated with type 2 immunity, such as type 2 innate lymphoid cells (ILC2), eosinophils, M2-polarized macrophages and T helper type 2 (Th2) cells, are also important regulators of adipose tissue homeostasis and wound healing. Our research aims to find novel regulatory mechanisms, which we want to exploit to improve therapeutic interventions during acute and chronic inflammatory conditions.
Obesity
Image published in: Schwartz C, et al. Innate PD-L1 limits T cell–mediated adipose tissue inflammation and ameliorates diet-induced obesity. Science Translational Medicine, 2022
During obesity the homeostatic anti-inflammatory immune environment within the adipose tissue is replaced by pro-inflammatory cells, including Th1 and Th17 cells and M1 macrophages. We have discovered that the immune checkpoint protein PD-L1 on dendritic cells (DC) plays an important role in limiting the pro-inflammatory response and thus ameliorates weight gain and metabolic health.
Wound healing
Wound healing is a tightly regulated process to repair tissue while fighting off pathogens. Obesity is associated with an increased risk to develop wound infections, which may lead to the prolonged persistence of pathogens and the development of chronic inflammation. Type 2 immune cells - in particular M2 macrophages, ILC2 and Th2 cells - are critically involved in this process. Thus, we aim to understand the mechansims that lead to their dysfunction during obesity.
Atopic dermatitis
Image published in: Hawerkamp HC, Fahy CMR, Fallon PG, Schwartz C. Break on through: The role of innate immunity and barrier defence in atopic dermatitis and psoriasis. Skin Health and Disease, 2022
Atopic dermatitis (AD) is an important allergic disease of the skin. Here, type 2 immune responses play a detrimental role through the production of IgE directed against normally harmless antigens. One of many factors leading to the development of AD is the breakdown of the skin barrier, which allows for penetration of antigens (and pathogens!) into deeper layers of the skin, where an inflammatory response is elicited. We are interested in the role of type 2 associated cells in the maintenance of skin barrier integrity.
Infections
Image published in: Schwartz C, Hams E, Fallon PG. Helminth Modulation of Lung Inflammation. Trends in Parasitology, 2018
Immune responses against parasitic worms (helminths) generally require a functional type 2 immune response. Many cell types, including ILC2, eosinophils, Th2 cells, macrophages and others, form a dynamically changing immune response that determines the outcome (immunopathology - pathogen elimination - chronic persistence/tolerance) of the infection.
Chronic airway inflammation
Airway hypersensitivity can present itself in many forms - the most commonly known may be asthma, which can have an allergic or non-allergic etiology. Over the past decades it became clear that different underlying immune responses - endotypes - cause different forms of airway inflammation. While there are novel therapeutics targeting type 2 high endotypes, only limited treatment options for non-T2 or mixed endotypes exist. Thus, we want to understand the underlying mechanisms during non-T2 airway inflammation and how we can therapeutically target effector cells, such as alveolar macrophages, Th1 or Th17 cells to alleviate lung pathology, particularly in chronic states.
Image published in: Schwartz C, Fallon PG. The high and lows of type 2 asthma and mouse models. Journal of Allergy and Clinical Investigation, Editorial, 2020
Microbiome changes
The role of the microbiota in shaping immune responses is an important field of research. On the one hand, obesity, infections and dermatitis can influence the microbiome (both gut and skin), while the microbiome itself influences the onset, severity, chronicity and outcome of these conditions in part through metabolic products. Therefore, analysis of the microbiome both in mice and patients accompanies our research projects.
Methods
Flow cytometry
Immunofluorescence microscopy
RNA sequencing
16S rRNA sequencing
Clinical samples
Animal models
Cell culture
Inflammation models
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