H2020Индивидуална стипендия2020–2022

Retinoic AC-DC · Role of Retinoic Acid signaling in cDC1 and cDC2 on intestinal immune homeostasis and disease

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-01-01 → 2022-04-25
Финансиране от ЕС: 191 852 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Ретиноичната киселина (производно на витамин А) и нейният ефект върху два вида дендритни клетки в червата се анализират в този проект. Разбирането на тези процеси помага да се разбере как се развиват възпалителните заболявания на червата.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

The intestinal mucosa is the largest surface of the body in contact with the external environment and is constantly exposed to foreign antigens and metabolites derived from the diet and resident microbiota. The intestinal microbiota is essential to our health, and continual and mutualistic dialogue between the microbiota and the intestinal immune system is required to maintain tissue homeostasis. Breakdown in such crosstalk, for example from nutritional deficiencies or microbiota alterations (dysbiosis), can rewire immune cell development and function, contributing to Inflammatory Bowel Disease (IBD). Conventional dendritic cells (cDC) are the key antigen presenting cells of the immune system, essential for the initiation and regulation of adaptive immune responses. cDC comprise of two major subsets, cDC1 and cDC2 and we have previously shown that intestinal these subsets play distinct non-redundant roles in intestinal adaptive immune responses. It is also becoming increasingly clear that the phenotype and function of cDC is regulated by signals these cells receive within their local tissue environment. Identifying such environmental factors and the underlying mechanisms by which they regulate cDC function may provide opportunities to regulate cDC dependent immune responses for the benefit of human health. The dietary derived Vitamin A metabolite, retinoic acid (RA) is a major immune modulator, in particular in the small intestine, where its concentrations are highest. We have shown that cDC receive RA signals within the small intestine however the impact of such signaling on cDC transcription and function is unclear. The overall objective of the project was to understand the impact of RA signaling on intestinal cDC1 and cDC2 transcription, phenotype and function in vivo and its importance in small intestinal immune homeostasis.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

LUNDS UNIVERSITET · LundКоординаторШвеция