At the mucosal surfaces of the airways, intestine, and urogenital tract, the separation of our body from the environment is at times only one cell wide. These surfaces are colonized by a diverse mixture of microbial organisms, which under normal conditions, evolved to be beneficial. However, the mucosal surfaces are also a common entry point for pathogens and toxins. Therefore, the mucosal immune system has to fulfill two often-conflicting functions: to protect the host from harmful invaders, like pathogen; and support the function of the mucosa and to ensure the peaceful cooperation with the commensal microbiota. When this balance is disturbed, diseases are usually the consequence.
Our laboratory wants to better understand how the various immune cells in and around the mucosa cooperate to maintain its function and health. A particular focus is placed on innate-like T cells, iNKT and MAIT cells, which are innate memory T cells with several unique features (Wingender & Kronenberg 2020, Hapil & Wingender 2018). In our translational approach, we combine work with clinical samples, advanced in vitro models, and in vivo mouse models, to develop novel diagnostic and therapeutic applications.
1) The role of innate-like T cells in asthma and COPD: 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.
2) Impact of the intestinal microbiota on the adipose tissue: We previously showed that iNKT cells are impacted by the intestinal microbiota (Wei et al. 2010, Wingender et al. 2012, Wingender 2016) and that antigenic challenge of iNKT cells leads to long-lasting changes in the adipose tissue (Sag et al. 2014). We currently investigate how the adipose tissue is affected by translocation of intestinal bacteria into the peritoneum.
· Death receptors: We investigate the role of TRAIL and DR4/DR5 interaction for the anti-tumor response of iNKT cells, in particular in the context of MM (multiple myeloma) and AML (acute myelogenous leukemia) (Sag et al. 2019).
· 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, 2015b). 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 development and function of NKT2 and NKTFH cells.
· Rare diseases: IBG recently was awarded an ERA Chair project to establish itself as a Center of Excellence for Rare Disease research. 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.
Chandra S*, Wingender G*, Greenbaum JA*, Lail A, Khurana A, Moghasddasi A, Rosenbach M, Jaffee K, Gern JE, Wood R, O'Connor G, Sandel M, Kattan M, Bacharier L, Togias A, Visness C, Horner AA, & Kronenberg M: Allergy and asthma in inner-city children: possible roles of MAIT cells and variation in the home environment; 2018, J Immunol, 200: 1995-2000. (*contributed equally)
Hapil FZ & Wingender G: Interaction between iNKT cells and the mucosal microbiota; 2018, Immunology; 155:164-175.
Sag D, Ayyildiz ZO, Günalp S, Wingender G: The role of TRAIL/DRs in the modulation of immune cells and responses; 2019, Cancers, 11:1469.
Sag D, Krause P, Hedrick CC, Kronenberg M, Wingender G: IL-10-producing NKT10 cells are a distinct regulatory invariant NKT cell subset; 2014, J Clin Invest; 124, 3725-3740.
Wei B, Wingender G, Fujiwara D, Chen DY, McPherson M, Brewer S, Kronenberg M, Braun J: Commensal microbiota and CD8+ T cells shape the formation of invariant NKT cells; 2010, J Immunol, 184, 1218-1226.
Wingender G* & Kronenberg M: Chapter 7: The role of invariant Natural Killer T cells in autoimmune diseases; In: The Autoimmune Diseases (6th edition), 2020; edited by Noel R. Rose and Ian R. Mackay, 117-153. (*Corresponding authors).
Wingender G: From the deep sea to everywhere: Environmental antigens for iNKT cells; 2016, Arch Immunol Ther Exp, 64: 291-298.
Wingender G, Sag D, Kronenberg M: NKT10 cells: a novel iNKT cell subset; 2015a, Oncotarget, 6: 26552-26553.
Wingender G, Birkholz A, Sag D, Farber E, Chitale S, Howell AR, Kronenberg M: Selective conditions are required for the induction of iNKT cell hypo-responsiveness by antigenic stimulation; 2015b, J Immunol, 195: 3838-3848.
Wingender G, Stepniak D, Krebs P, McBride S, Mazmanian S.K., Kronenberg M: Intestinal microbes modulate the phenotype and function of mouse invariant natural killer T cells; 2012, Gastroenterology, 143, 418-428.
Wingender G, Rogers P, Batzer G, Lee MS, Bai D, Pei B, Khurana A, Kronenberg M, Horner AA: Invariant NKT cells are required for airway inflammation induced by environmental antigens; 2011, J Exp Med, 208, 1151-1162.
The Scientific and Technological Research Council of Turkey (TUBITAK) - RD : Characteristics And Plasticity of INKT Cell Subsets In Mouse And Human
European Molecular Biology Organization (EMBO) - RD : Regulation of Airway Inflammations By Invariant Natural Killer T (INKT) Cells During Allergen Induced Hypersensitivity And Infection
The Scientific and Technological Research Council of Turkey (TUBITAK) - RD : Functional characteristics and transcription factor usage of mouse NKT10 cells
The Scientific and Technological Research Council of Turkey (TUBITAK) - RD : Cell-cell interactions of iNKT cells during airway hypersensitivity responses
European Union - RD : Death Receptor Signalling in Tumour Immune Editing
DEÜ BAP - Dokuz Eylul University Scientific Research Projects Coordination Unit - RD : Implementing technologies and methodologies for the investigation of invariant Natural Killer T (iNKT) cells
DEÜ BAP - Dokuz Eylul University Scientific Research Projects Coordination Unit - RD : İnvariyant Doğal Öldürücü T (iNKT) hücrelerinin alerjen kaynaklı akciğere infiltrasyonu / Allergen induced lung infiltration of invariant Natural Killer (iNKT) cells
The Scientific and Technological Research Council of Turkey (TUBITAK) - RD : The role of TRAIL mediated signals on the proliferation and function of human iNKT cells
DEÜ BAP - Dokuz Eylul University Scientific Research Projects Coordination Unit - RD : The role of invariant natural killer T (iNKT) cells in neutrophilic, Th1-driven, asthma
Our laboratory always considers qualified applications of prospective graduate students (Ph.D.) and of post-doctoral fellows with a strong background in immunology or bioinformatics. If you are interested in advancing immunology in a top-notch, collaborative environment, then please contact Gerhard Wingender directly (email@example.com) with your CV and letter of motivation.