Employees of the Department for Immunology have been rewarded the funding for a project "Modulation of gut ILC3 by a FFAR2 agonist for the treatment of autoimmune diseases" GUTtoAID. The duration of the project will be three years..

Abstrakt

The number of individuals affected by autoimmune diseases (AID) is steadily increasing in modern societies. AID lessen the life quality of the affected persons and their families and contribute to the economic burden of society. Two typical organ-specific AID will be investigated in this project: type 1 diabetes (T1D) and multiple sclerosis (MS), in which pancreas and the central nervous system (CNS), respectively, are targeted by autoimmunity. Recent studies identify gut-associated immune tissue as a potential site of AID initiation and a possible target for AID modulation/therapy. Gut type 3 innate lymphoid cells (ILC3) are especially appealing to be targeted in AID as they acquire environmental cues from the gut lumen and maintain gut homeostasis by shaping the local immune response. Notably, ILC3 stimulate regulatory T cells (Treg) in response to shortchain fatty acids (SCFA). Having in mind that agonist of free fatty acid receptor 2 (FFAR2) (Compound-1) was reported to selectively promote the beneficial function of gut ILC3 in inflammatory bowel disease, we hypothesize that Compound-1 will attenuate autoimmune diseases studied in the animal models of T1D (NOD mice and streptozotocin-induced diabetes) and MS (experimental autoimmune encephalomyelitis – EAE). Besides the evaluation of the impact of Compound-1 on the clinical manifestations of the diseases, its effects on the immune response in the gut, as well as in the target tissues (pancreas and CNS) will be assessed. Further, our preliminary findings show a significant decrease in the proportion of a Treg-inducing subset of IL- 2+ ILC3 in the gut during T1D and EAE. Also, reduction in the expression of the major ILC3 gut homeostasis cytokine IL-22 is observed. Therefore, this study will be focused on ILC3 and Treg, and on the role of IL-22 and IL-2-producing ILC3 in Compound 1-instigated beneficial effects on T1D and EAE. The results of the study will determine the potential of Compound-1 to act through ILC3 to diminish autoimmunity in T1D and EAE. As T1D and MS, alike most of AID are incurable diseases, the long-term goal of this project is to incite clinical research on FFAR2-based ILC3 modulation for the benefit of the patients affected by these diseases.

Project leader: Dr. Đorđe Miljković

Team members:
Dr. Ivana Stojanović
Dr. Tamara Saksida
Dr. Bojan Jevtić
Dr. Nada Pejnović
Dr. Mirjana Dimitrijević
Dr. Miljana Momčilović
Dr. Suzana Stanisavljević
Dr. Neda Đedović
Dr. Ivan Koprivica
Milica Lazarević
Dragica Gajić