TISSUENEU · Role of infiltrating neutrophils in tissue homeostasis
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-05-01 → 2019-04-30
- EU contribution
- €158,122
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Role of infiltrating neutrophils in tissue homeostasis
Neutrophils are immune cells endowed with the capacity to infiltrate multiple tissues during inflammation to fight against pathogens. However, these cells continuously infiltrate most tissues also during steady state. Whereas several studies have addressed neutrophil biology in infiltrated tissues during pathological conditions, it is currently unknown how homeostatic infiltration of neutrophils modulates their behaviour and function and how this could affect the physiology of their targeted tissues. Tissueneu aim to explore neutrophil heterogeneity in tissues during homeostasis and to identify novel functions in these leukocytes that go beyond their role as immune sentinels. Understanding neutrophils heterogeneity and its impact in tissue physiology is of the utmost importance because different types of neutrophils act as disease-modifying factor in several pathological conditions including cancer, stroke, myocardial infarction, autoimmune disease or tuberculosis. In this research project, we aim to provide a characterization of neutrophil heterogeneity and function during homeostasis. This information will provide a molecular and functional roadtrip of neutrophils biology during health that is currently missing, and will allow exploring how disease shape this heterogeneity and how this affect tissue homeostasis. Our final aim to identify the molecular mechanisms that modulate neutrophil diversity and to develop novel therapeutic approaches to fight disease.
Data: CORDIS, © European Union
Project objective
Neutrophils follow daily cycles of release from and migration back into the bone marrow, where they are eliminated. After searching for the presence of neutrophils across multiple tissues of healthy mice under steady state, my host laboratory found neutrophils in most of the tissue analyzed. These findings require the study of the role of neutrophils in their tissue of destination. Several studies have shown that neutrophil clearance might be a significant source of homeostatic signals able to functionally modulate the tissues and organs where they are eliminated. In addition, specific functions for neutrophils in the spleen have already been described. I hypothesize that neutrophils may have important roles for the homeostasis and functioning of the tissues that they infiltrate, and that they acquire tissue-specific phenotypes that favor their local functions.To understand neutrophil homeostatic functions within the tissue, I will first characterize the transcriptome of 7 different subsets of neutrophils population from intestine, lung, muscle, skin, spleen, blood and bone marrow by RNA-sequencing. In addition, to investigate weather neutrophil heterogeneity within the tissues is a stochastic or a tissue-educated mechanism I will perform single cell RNA sequencing (sc-RNA-seq) of blood neutrophils to characterize the presence of a neutrophil tissue-specific signature in the blood. Moreover, I will combine next generation sequencing techniques with the use of different transgenic mouse models to uncover tissue specific regenerative functions of neutrophils in the skeletal muscle and the skin. Results obtained in this proposal aim to challenge the classical conception about neutrophils as a homogenous population of terminally differentiated cells with functions restricted to inflammation and to explore their hetroogeneity and expand our knowledge about their specific functions during tissue homeostasis.
Original text from CORDIS.
Participants
- CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) · MadridCoordinatorSpain
Links
Data: CORDIS, © European Union