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Role of Retinoic Acid signaling in cDC1 and cDC2 on intestinal immune homeostasis and disease

Project description

Retinoic acid effect on intestinal immune cells

The intestine is exposed to more antigens than any organ in the body. This complex environment includes the products of digestion along with its own healthy bacteria and foreign pathogens. The unique mucosal immune system must balance protection against infection without starting a destructive war against its normal microbiota. Vitamin A in the form of retinoic acid has specific effects on intestinal immune cells. However, these cells are not a homogeneous population and it is not clear what the effects of retinoic acid are on various subsets. The Retinoic AC-DC project is seeking an answer to this open question using high-tech methods to study the immune cells in both normal and pathologic states.

Objective

For the past years, it has become undeniable that environmental signals have a great impact on the intestinal immune system. Among them, the Vitamin A (Vit A) has a central role in intestinal immunity. Consequently, the Vit A deficiency (VAD) is associated with an increase of infectious diseases and the supplementation of Vit A to pregnant mothers and children is a protocol defined by the World Health Organization. The vit A is mostly absorbed in the small intestine and derived into Retinoic Acid (RA), especially by conventional dendritic cells (cDC). Studies on the impact of RA on intestinal immunity, including in the host laboratory, have highlighted a major impact of RA produced by cDC on the homing and the polarization of effectors cells, although the effect of the RA on specific cDC subsets remains unknown. The understanding of this effect is an essential step for manipulating the system while avoiding secondary effects, usually triggered by impacting such central metabolites as RA. We propose to define this specific action of the RA on cDC using cutting edge technologies and state of art techniques both developed in the laboratory and brought by the candidate. These techniques will allow the investigation of the RA effect on specific intestinal cDC subsets at transcriptomic and phenotypic levels under homeostatic and pathologic states. The host laboratory will develop the professional skills of the candidate by reinforcing his individual competences, including laboratory techniques, writing, critical and innovative thinking, and communication abilities. Those will be further enhanced by the participation to many national and international collaborations enabled by Dr. Agace’s strong network. The high-quality infrastructure provided to the candidate and his complementary profile and techniques, acquired during his PhD, will ensure a solid project development and allow him to acquire all the abilities needed to become an efficient independent researcher.

Coordinator

LUNDS UNIVERSITET
Net EU contribution
€ 191 852,16
Address
Paradisgatan 5c
22100 Lund
Sweden

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Region
Södra Sverige Sydsverige Skåne län
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 191 852,16