Periodic Reporting for period 4 - ENVIROIMMUNE (Environmental modulators of the immune cell balance in health and disease)
Reporting period: 2018-11-01 to 2020-07-31
In summary, the project was successful and we were able to gain new scientific insights how high-salt intake and changes in the ionic microenvironment directly and indirectly could impact the immune cell balance and models of disease. Thereby the action contributed to a better understanding how environmental factors may shape immune responses. Current major conclusions derived from the project are that a) the immune cell balance could be directly impacted by high-salt conditions through several layers of mechanism including alterations in immunometabolic states and b) that excess-salt intake could lead to shifts in the gut microbiota and thereby indirectly affects immune responses and models of disease, likely by altering abundance of bacterial derived immuno-modulatory metabolites.
In the framework of part 1 of the project we studied direct effects of high-salt conditions of human T cell subsets. By analysing global salt-induced molecular changes of in cell culture activated Th17 and Tregs and subsequent functional analysis by cell culture based assays and by using experimental models of disease, we were able to discover new pathways how changes in the ionic microenvironment affect T cell responses. A highly interesting aspect was the interference of salt with immunometabolism of T cells and subsequent impact on function, mimicking dysfunctional T cells found in patients with autoimmunity. These results are currently under further investigation to understand if it relates to human disease. Moreover, based on the huge set of generated data, analysis and exploitation of other pathways will be continued in the future.
In part 2 of the project we investigated potential indirect effects of high-salt intake on the immune cell balance, particularly concentrating on the gut microbiome. It is now well accepted that immune system and microbial communities residing in the gut are tightly interconnected and that changes in these gut microbial communities can have a major impact on the immune cell balance and disease. Together with our collaborators we discovered that high-salt intake indeed could impact gut microbial communities and thereby also indirectly modulate the immune cell balance and disease, as demonstrated in e.g. models of neuroinflammation. Based on collecting data from further experiments by modulating salt-intake we gained by now a clearer view on salt-induced changes on the gut microbiome and are currently analysing its impact on immune function and relation to disease in follow up studies.
Taken together the project contributed significantly to a better knowledge about the impact of environmental factors on the immune cell balance and disease. Our findings added novel insights into crucial mechanisms how sodium could modulate immune function by direct and indirect mechanism and thus may contribute to the future development of novel treatment and prevention strategies for diseases. Under the support of the ERC project several manuscripts were already published or submitted for publication and based on follow up studies we foresee further dissemination of data and findings based on the project.