KCs and Gut Antigens · Elucidating the role of liver resident Kupffer cells in the regulation of the immune responses to intestinal antigens
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-05-01 → 2017-04-30
- EU contribution
- €160,800
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Elucidating the role of liver resident Kupffer cells in the regulation of the immune responses to intestinal antigens
Food allergies and inflammatory bowel diseases are increasing health problems in industrialized countries. These diseases result from an abnormality in the way the immune system reacts to harmless materials in our gut such as foods and friendly bacteria. To be able to design new and improved ways of treating or preventing these disorders, we must first understand the processes that usually prevent them in healthy individuals. The liver drains all the blood coming from the intestine and has long been thought to be important in controlling immune responses to these materials. However, the precise cell(s) involved, or the underlying molecular mechanisms are still unknown. This project aimed to address this gap in our knowledge by generating and applying new methods to study Kupffer cells (KCs), which are not only the most abundant immune cells in the liver but also the first immune cells to be in contact with materials entering the liver from the intestine as they reside in the blood flow in the liver sinusoids. We also aimed to assess how KCs influence the other immune cells involved in instructing immune responses to such agents.
Data: CORDIS, © European Union
Project objective
The liver is constantly exposed to intestinal material via portal blood circulation and thus it has long been implicated in the modulation of systemic immune responses to intestinal antigens. Despite this, the precise cells involved and the molecular mechanisms at play are largely unknown. Liver resident macrophages termed Kupffer cells (KCs) are ideally located within the blood stream of the liver sinusoids to encounter intestinal antigens. We hypothesise that KCs acquire intestinal antigens and subsequently modulate the immune response to these. Despite indications that KCs are involved, the lack of KC-specific tools has significantly hampered the study of these cells and to date their physiological role in modulating immune responses to intestinal antigens remains unclear. Here we propose to utilize novel and innovative tools including KC-specific knock-in (KI) mice generated by the host lab to specifically examine the role of KCs in antigen acquisition, presentation and determination of T cell fate. To our knowledge these tools represent the first of their kind and place us in a unique position to specifically examine the role of KCs in regulating the immune response to intestinal antigens. By combining murine modeling with analysis of human tissues in collaboration with the University Hospital, this project will greatly advance our understanding of the role of KCs and potentially uncover new therapeutic strategies in the prevention and/or treatment of disorders where the systemic immune response to intestinal antigens is dysregulated such as food allergies and inflammatory bowel diseases (IBDs).
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
Data: CORDIS, © European Union