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General project overview

Further information
Prof. dr. Rudi Hendriks, Head of the Research Laboratory,
e-mail: r.hendriks@erasmusmc.nl

 Duration Yes/NoAvailable per (date) 
 6 months Yes/No See individual projects
 12 months  Yes/No See individual projects
 18 months Yes/No See individual projects


Background
The adaptive immune response provides humans with B and T lymphocytes that carry immunoreceptors that are highly specific for antigens that these cells have not encountered before. Dendritic cells (DCs) are professional antigen-presenting cells (APC) that are located at sites where maximal microbial encounter occurs. They are essential for the transport of antigens (from the airway mucosa and interstitium to the draining lymph nodes) and thereby initiate the activation of lymphocytes. In this way, the adaptive immune system has the capacity to strengthen and to regulate the innate defense mechanisms and to build specific immunological memory so that subsequent challenges with the same pathogen are efficiently overcome. The lung is continuously exposed to the outside world and is a portal of entry for viral, bacterial, and fungal infection. Throughout evolution, an extensive defense mechanism has been developed that protects humans from these potentially lethal assaults and at the same prevents reactivity to harmless antigens. Nevertheless, the incidence of lung diseases such as asthma and sarcoidosis has risen dramatically over the last 50 years and pneumonia is a leading cause of death among young children and the elderly worldwide.
 
Research
The research aims in the Department of Pulmonary Medicine comprise:

  • To elucidate the role of DCs in directing and maintaining an acute or chronic localized immune response in the lung, e.g. in asthma, pulmonary hypertension, sarcoidosis and other interstitial lung diseases.
  • To develop DC-based immunotherapy with tumor-pulsed autologous DCs to prevent mesothelioma recurrences. This approach is based on the observation that DCs are able to induce protective immunity in a mouse model of mesothelioma. In this context, we also aim to investigate how the effects of negative regulators of these responses, including myeloid-derived suppressor cells and regulatory T cells can be dampened.
  • To study the role of effector T cells and innate lymphoid cells in various pathological conditions, including asthma, sarcoidosis, influenza infection and pneumonia.
  • To identify the molecular mechanisms involved in B cell repertoire selection, B cell activation and - in particular - B cell receptor signaling, both in systemic autoimmune disease, such as Sjogren syndrome and rheumatoid arthritis, and interstitial lung diseases that often have an autoimmune component.

 
Molecular approaches become increasingly important to unravel the pathogenesis of pulmonary diseases. Over the last years technical expertise has been acquired in mouse models for various diseases, including asthma, influenza, interstitial lung disease, pulmonary hypertension and lung berylliosis. Animal models have been generated with specific immune defects (in DC, or activation or development of B, T or innate lymphocytes). In addition, several projects in the lab include human studies, using patient material. We make use of various assays for humoral and cellular immunity, multi-color flow cytometry and cell sorting, immunohistochemistry, molecular biology, genome-wide expression and epigenetic analyses, chromatin immunoprecipitation, protein biochemistry and retroviral transduction.

Collaborations
We have fruitful collaborations with various research groups at the Erasmus MC (Departments of Cell Biology, Genetics, Virology, Immunology, Pediatrics) and outside the Erasmus MC (UMCG Groningen, University of Ghent, Belgium; University of Freiburg, Germany; University hospital Ulm, Germany; Medical University of Vienna, Austria; Institut Pasteur, Paris, France). 

Projects
Projects are available in various research groups in the laboratory.

Project 1: Pulmonary hypertension: a decisive role for the A20 enzyme in dendritic cells
Project 2: Modulation of the immune system for personalized cancer treatment in patients with thoracic malignancies
Project 3: B cell receptor signaling in auto-immune disease
Project 4: Innate lymphoid cells: identification of their role in allergic asthma and exacerbations upon respiratory tract infection


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