Background and current state of research
In modern developed countries, the incidence of autoimmune diseases increased constantly in the past decades, becoming a major clinical burden. However, their incidence in developing countries remains low, whereas in first-generation immigrants it almost reaches the level of the indigenous population. This observation points towards the contribution of environmental factors, such as infections, diet and medication, among many others. Several theories to explain the impact of environmental factors have been proposed; however, the exact mechanisms of this gene-environment interaction still remain unknown.
Despite major progress in utilizing genome-wide association studies in patient cohorts and mouse models to identify new susceptibility genes for autoimmune diseases, some aspects of their genetics remain unclear. Some genetic polymorphisms in lupus-associated genes, such as HLA, cytokines or complement system have been described; however, the mechanisms by which these factors can influence the onset of the disease are still not completely understood.
To address the question whether diet influences the inflammatory phenotypes, we used an autoimmune-prone advanced intercross (AIL) mouse line here that was previously created in our lab.
Our goals
In a previous project by Artem Vorobyev’s RTG1743, a total of 1,237 AIL mice from 4 generations (G15, G18, G19, G20) were fed different diets (control diet, Western diet and calorie-restricted diet). 1,154 mice survived the 6-month observation period and were genotyped. All 302 mice from the 15th generation were fed standard mouse chow, while 336 mice from the 18th-20th generation were fed a Western diet, 349 a calorie-reduced diet and 250 standard mouse chow ad lib. Organs from 1,154 mice were used for phenotyping and the serum was taken for further analysis in the present project.
Using the serum samples of these 1,154 AIL mice, we would like to:
- analyze the serum C-reactive protein (CRP) as a marker for general inflammation,
- investigate different serum cytokines (IL-1ß, IL-23, TNFa, IL-10, IL-17A, IL-4) to analyze the correlation between diet and cytokine expression,
- use statistical methods to identify the interplay between inflammation markers (exemplified by CRP), cytokine expression and diet that influence the inflammatory phenotypes in AIL mice.