The immune and endocrine systems are intricately linked. In response to infection the immune system mediates metabolic changes in our body, generally referred to as sickness behavior, by adjusting endocrine signaling, with the purpose to better fight infection. Conversely, endocrine hormones have a profound impact on immune cells to ensure that their consumption is adjusted to the systemic availability. However, much of the immunomodulatory effects of hormones is unknown. This is of particular importance in for patients with metabolic disease such as Type 2 diabetes (T2D), who have endocrine dysregulation and are also more susceptible to infection. CD8 T cells express very high levels of the receptors for the endocrine hormone adiponectin and our preliminary data indicates that this adipose tissue-derived hormone promotes memory cell formation. In this project we will investigate the specific effect of adiponectin on memory CD8 T cells and whether it plays a role in immune cell dysfunction in context of T2D. By using established in vitro and in vivo models in combination with genetically modified mice, we will determine the specific role of this hormone in memory cells. With a combination of advanced proteomics, transcriptomics and metabolomics, we will elucidate the molecular mechanisms via which this factor mediates its effect in memory cells. With our established mouse models for metabolic disease, we will determine the specific role of adiponectin in memory CD8 T cell disfunction in context of T2D. Finally, by analyzing cells from healthy human volunteers, as well as of patients with T2D, we will confirm the relevance of our findings for the human situation. In summary, our project will shed important new light on immune-endocrine interactions in health and in context of metabolic disease.
Project name: The role of adiponectin in CD8 T cell biology
Project identifier: IP-2022-10-3414
Project duration: 18.12.2023 - 17.12.2027
Project budget: EUR 199.083
Funding body: Croatian Science Foundation / Hrvatska zaklada za Znanost (HRZZ)