Impact of Semaphorin 7A on the Control of Inflammation-Resolution Programs

• Applicant: Professorin Dr. Valbona Mirakaj
• Subject Area: Anaesthesiology
• Term: from 2016 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 320501009

Acute inflammation, which is part of the complex response to tissue injury or infection by invading microorganism, is classified into an initial and a resolution phase. A critical step in the initial immune response is the control of leukocyte migration, and if failed, inflammation can become chronic leading to collateral tissue destruction and loss of functional organ integrity. Resolution of an acute inflammatory response is fundamental to return affected tissues to homeostasis. Cardinal signs of resolution are cessation of neutrophil influx, the counterregulation of pro-inflammatory mediators, apoptosis of PMN, the active clearance of apoptotic cells and invading microorganism. Specialized pro-resolving lipid mediators (SPM) named lipoxins, resolvins, protectins and maresins are essential for the control of resolution mechanisms. Neuronal guidance proteins (NGP) have been identified to play a crucial role in the initial phase of an acute inflammatory response. Hence, their role in resolving actions is to date not clarified. In preliminary experiments we found that the neuronal guidance protein Semaphorin 7A (Sema7A) contributes to resolution programs of an acute inflammatory response. The aim of this grant proposal is to explore the impact of Sema7A and its target receptor PlexinC1 on the biosynthesis of specialized pro-resolving mediators, the interaction of leukocytes in the dynamic process and the procedure of clearance. We will elucidate the role of myeloid derived Sema7A and its target receptor PlexinC1 using Cre/loxP conditional gene deletion techniques. The results generated from the proposed aims will contribute to a deeper understanding of the link between the neuronal guidance protein system and the resolution of an inflammatory process. This will potentially open novel therapeutic options in the treatment of patients suffering from critical illnesses.

• DFG Programme: Research Grants