The role of CCL22 chemokine expression in the maintenance of immune homeostasis

• Applicant: Professor Dr. David Anz
• Subject Area: Immunology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 424603761

The human immune system is a very complex network responsible for the protection from pathogens and the destruction of abnormal tissue. The ability to recognise foreign substances while maintaining tolerance for body’s own structures is an essential prerequisite. A key player of immunological self-tolerance is a subtype of the CD4+ T cells, the regulatory T cells (Tregs), which are capable to supress adaptive and innate immune cells in their immunological action. The variety of mechanisms applied by Tregs for this task can serve as targets for therapeutic intervention. We and others, could show, that CCL22 significantly contributes to the recruitment of Tregs. The Knock-out Mouse Project (KOMP) of the National Institute of Health was able to generate a completely CCL22-deficient mouse. Our unpublished results using this mouse showed that CCL22 is crucially involved in contact formation between Tregs and dendritic cells (DCs) in the lymph node, thus supressing T cell immune response. This contact formation between Tregs and DCs is essential for the maintenance of peripheral tolerance. Therefore, our observations suggest that CCL22 holds an important regulatory function in the development of T cell immunity. The aim of this project is to evaluate the role of CCL22 in the development of autoimmunity by combining the CCL22 deficient mice with different murine autoimmune disease models. In detail we will investigate autoimmunity in the murine lupus erythematodes model under CCL22 deficient and proficient conditions. Further the development of autoimmune diabetes in two different murine models will be evaluated on their CCL22 dependency. In both autoimmune disease models, it will also be investigated whether artificial systemic overexpression of CCL22 can influence the course of the disease. In summary, our investigations are aimed to improve the understanding of the role of CCL22 in the development of adaptive immunity and autoimmunity. Therapeutic concepts, targeting cytokines, receptors and other signalling molecules are currently very successful in the clinic. Our work can help to evaluate the role of CCL22 as a possible target for future immunotherapeutic interventions.

• DFG Programme: Research Grants