Objective The role of chronic inflammation in obesity, metabolic and cardiovascular diseases is increasingly recognized. Bile acids (BA), synthesized in the liver and modified by the gut flora, facilitate lipid absorption in the intestine. BA modulate lipid and glucose homeostasis by activating the nuclear receptor FXR and the GPCR TGR5. Intriguingly, peripheral BA concentrations are elevated in type 2 diabetes (T2D) and FXR mediates the beneficial metabolic response to gastric bypass in mice. The immune system plays an important role in the cross-talk with metabolic tissues, such as liver, intestine and adipose tissues. However, whether BA modulate immune cell function is unknown. Our unpublished results identifying FXR and TGR5 expression in lymphoid cells, prompt us to study their role in the regulation of glucose and lipid metabolism through immune cell modulation. Using reporter mice and specific ligands, we will characterize the immune cells expressing active FXR and TGR5. We will determine their role in metabolism and inflammation by immune cell-specific gene inactivation in models of obesity, T2D and elevated peripheral blood BA concentrations. Mass cytometry, cell sorting and single cell transcriptomic analysis will allow the identification of gene networks regulated by BA and their receptors. As microbiota generate biologically active secondary BA, we will assess the impact of microbiota depletion and subsequent BA acid pool modifications on immune cell populations. Translational studies in humans with altered BA metabolism and pharmacological treatment with anti-diabetic BA sequestrants will allow assessment of alterations in immune functions. This project aims to identify an hitherto unexplored role of BA through modulation of the immune system on T2D, NAFLD and dyslipidemia. Success of the project critically depends on an integrative approach uniquely undertaken in my laboratory through its unique multidisciplinary expertise in basic and translational biology. Fields of science medical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicinecardiologycardiovascular diseases Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-ADG-2015 - ERC Advanced Grant Call for proposal ERC-2015-AdG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution UNIVERSITE DE LILLE Net EU contribution € 1 724 306,25 Address 42 RUE PAUL DUEZ 59000 Lille France See on map Region Hauts-de-France Nord-Pas de Calais Nord Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 500 000,00 Beneficiaries (3) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITE DE LILLE France Net EU contribution € 1 724 306,25 Address 42 RUE PAUL DUEZ 59000 Lille See on map Region Hauts-de-France Nord-Pas de Calais Nord Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 500 000,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France Net EU contribution € 525 693,75 Address RUE DE TOLBIAC 101 75654 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 525 693,75 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. INSTITUT PASTEUR DE LILLE FONDATION France Net EU contribution € 250 000,00 Address RUE DU PROFESSEUR CALMETTE 1 59019 Lille See on map Region Hauts-de-France Nord-Pas de Calais Nord Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 250 000,00
