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

Descrizione del progetto

Effetto dell’acido retinoico sulle cellule immunitarie intestinali

L’intestino è esposto a molti più antigeni rispetto a qualsiasi altro organo del corpo. Questo complesso ambiente include i prodotti della digestione insieme ai propri batteri sani e ai patogeni estranei. L’esclusivo sistema immunitario della mucosa deve bilanciare la protezione dalle infezioni senza avviare una guerra distruttiva contro il suo normale microbiota. La vitamina A sotto forma di acido retinoico ha effetti specifici sulle cellule immunitarie intestinali. Tuttavia, queste cellule non rappresentano una popolazione omogenea e non è chiaro quali siano gli effetti dell’acido retinoico sui diversi sottogruppi. Il progetto Retinoic AC-DC sta cercando una risposta a questa domanda aperta utilizzando metodi ad alta tecnologia per studiare le cellule immunitarie sia in condizioni normali che patologiche.

Obiettivo

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.