Welcome to the Research Group Mucosal Immunology
The mucosal immune system of the gastrointestinal tract plays a dual and tightly regulated role in maintaining intestinal health: it serves as a crucial defense mechanism against pathogenic microbes and contributes to immune surveillance, eliminating potentially cancerous cells at an early stage. However, dysregulation of the mucosal immune system can induce pro-inflammatory conditions. Such exaggerated or chronic immune responses – often triggered by microbial imbalance (dysbiosis) or genetic susceptibility – can result in conditions such as inflammatory bowel disease (IBD). Over time, persistent inflammation can not only lead to the destruction of tissue architecture, but also create a microenvironment which promotes tumor development.
The group ›Mucosal Immunology‹ led by Professor Maximilian Waldner studies how immune responses in the gastrointestinal tract can be modified deliberately using cellular mechanics and aging-related mechanisms. For this, the scientists use advanced optical methods and systems biology approaches to investigate immune cell dynamics in the context of chronic mucosal inflammation and cancer development.
Research Overview
Immune cell mechanics in chronic mucosal inflammation
Immune cells are critical actors in the pathogenesis and progression of inflammatory bowel diseases (IBD). Specifically, immune cell trafficking is a key process which drives disease progression by recruiting immune cells to sites of inflammation. Notably, the mechanical properties of immune cells, such as size, deformability, and stiffness, influence their function and migration. Together with the division of Professor Jochen Guck, the RG Waldner is investigating these mechanical properties using Real Time Deformability Cytometry (RT-DC) – a method for high-throughput phenotyping – in the context of IBD. The aim of the project is to identify molecular mechanisms which regulate innate immune cell mechanics during mucosal inflammation and can be targeted for use in a new therapeutic strategy.
Aging-related mechanisms of T cell dysfunction in mucosal immunology
Aging is considered an important risk factor for a variety of conditions including inflammatory diseases and cancer. The mechanisms of aging are described as cellular and molecular changes which can affect the entire organism. Unsurprisingly, aging also impacts immune cell behaviors. Understanding aging-related mechanisms in T lymphocytes (T cells) is particularly important, as they are crucial mediators of IBD and colorectal cancer (CRC) development. Previous work by the research group showed that T cell aging phenotypes impact their dynamics in intestinal diseases such as IBD and CRC. These results pave the way towards understanding molecular signatures of dysfunctional T cells and developing novel targeted therapies for age-related diseases.
Label-free endoscopic microscopy of immune cell dynamics in the gastrointestinal tract
The microscopic intravital evaluation of immune responses in the digestive tract is a key requirement for deepening our knowledge about mechanisms of chronic mucosal inflammation and cancer development. Label-free multiphoton microscopy, based on the detection of autofluorescence and second harmonic generation signals enables the real-time characterization of tissue morphology without the need for staining procedures. Together with the group of Oliver Friedrich / Sebastian Schürmann (Institute of Medical Biotechnology, Friedrich-Alexander-Universität Erlangen-Nürnberg), the RG Waldner established a multiphoton endomicroscopy system which enables in vivo monitoring of immune cell dynamics in preclinical models of mucosal inflammation and cancer development.
Multi-cell epithelial monolayer used to study cell-cell interactions ex vivo
The intestinal barrier plays an important role in regulating interactions between the immune system and luminal factors, including microbiota and pathogens. Disruption in the epithelial barrier is often associated with an overreaction of the immune system, inducing inflammation and increased intestinal permeability. To investigate the mechanisms underlying epithelial barrier function and its role in immune interactions, the scientists developed an ex vivo epithelial monolayer system. This model closely mimics the structure and function of the intestinal barrier, allowing controlled studies of epithelial integrity, permeability, and the dynamic interactions between epithelial cells and immune cells in response to various stimuli such as bacterial infection.
Contact
Research Group Maximilian Waldner
Max-Planck-Zentrum für Physik und Medizin
Kussmaulallee 2
91054 Erlangen, Germany
maximilian.waldner@mpzpm.mpg.de
+49 9131 8284 177
Research team leader Prof. Maximilian Waldner