Research
Our laboratory investigates how innate-like T cells (iNKT cells, MAIT cells, γδ T cells) regulate immune responses in the lung and in the context of tumours. We utilize clinical samples, as well as advanced in vitro and in vivo mouse models, to better understand the underlying mechanisms. This is combined with in silico bioinformatic approaches. Our overall goal is to advance our understanding of innate-like T cells and to develop novel diagnostic and therapeutic applications.
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These are the current main research topics of the laboratory:
The role of innate-like T cells in the lung
iNKT cells play a potent, but surprisingly dichotomous role in lung inflammation. During infections, their Th1-response is protective, whereas during allergic responses, their Th2-response is deleterious. We previously demonstrated the role of iNKT and MAIT cells in allergic asthma (Chandra et al. 2018, Wingender et al. 2011). We currently study three distinct forms of airway inflammation, (i) eosinophilic and (ii) neutrophilic asthma, as well as (iii) COPD (chronic obstructive pulmonary disease), to understand how iNKT and MAIT cell responses in the lung are regulated with the ultimate goal to ameliorate these diseases. Furthermore, we investigate how iNKT cells in the lung can be utilized to boost local immune response, to be able to improve airway vaccination protocols.
The role of innate-like T cells in the adipose tissue
We previously showed that iNKT cells are impacted by the intestinal microbiota (Wingender et al. 2012, Hapil & Wingender 2018) and that antigenic challenge of iNKT cells leads to long-lasting changes in the adipose tissue (Sag et al. 2014). We currently investigate how innate-like T cells in the adipose tissue are affected by translocation of intestinal bacteria into the peritoneum and by the presence of gastrointestinal cancers. The omentum (a large adipose tissue within the human peritoneum), is the primary site of metastases of tumours of abdominal organs, which correlates with poor disease prognosis. This despite the fact that the omentum is enriched for innate-like T cells that are known to possess strong anti-tumour activity. We are trying to understand this seemingly functional impairment to find novel avenues to boost the anti-tumour activity of omental innate-like T cells.
iNKT cell subsets
Similar to conventional CD4+ T cells, iNKT cells can be divided into several functional subsets. We previously discovered a novel subset of iNKT cells with potent regulatory functions, called NKT10 cells due to their production of IL-10 (Sag et al. 2014, Wingender et al. 2015a). We are studying the in vivo regulation of these NKT10 cells in more detail and utilize preclinical studies to explore their therapeutic potential. Furthermore, ongoing projects investigate the development and function of NKT2 and NKTfh cells. In all cases, transcriptomics analysis compares the iNKT cell subsets with the corresponding CD4+ T cell subsets.
The role of death receptors (DRs) in the anti-tumor functions of innate-like T cells
We investigate the impact of TRAIL and DR4/DR5 interaction (Sag et al. 2019) on the anti-tumor response of innate-like T cells in the context of hemopoietic cancers using immunological and bioinformatics approaches. More details can be found on the project’s website (www.trail4life.eu/chiron).
Rare Diseases
With its ERA Chair project RareBoost (https://rareboost.ibg.edu.tr), IBG’s aims to establish itself as a Center of Excellence for Rare Disease research. Dr. Wingender is RareBoost’s Project Coordinator and in the context of this project, we currently launching a new line of research, focusing on rare diseases of the airways and of the immune system. More details can be found on the project’s website.