Project R-11560

Title

IL-13-overexpressing anti-inflammatory macrophages suppress trauma induced premature immune aging. (Research)

Abstract

Around 250.000 people get a spinal cord injury (SCI) annually worldwide. An epidemiological shift is occurring in the mean age of SCI patients, since the world consists of an increasingly active elderly population. The life expectancy of SCI patients is reduced compared to healthy individuals. Here, premature aging may play a role in different body systems like the cardiovascular system, the musculoskeletal system, the respiratory system, and the immune system. Thus far, aging of the immune system is widely accepted; however not much is known about (1) how SCI affects immune-aging and (2) how age affects SCI recovery. To answer the first question, age-related immune markers will be assessed in human SCI patients and a mouse SCI model at different time points after SCI. To answer the second question, functional recovery and alterations in intraspinal and/or systemic immune cell compartments will be analysed in young vs. old mice with SCI. In addition, promising strategies have been developed to suppress immune-aging. Previously, prof. Hendrix' lab developed macrophages (Mφs) that overexpress anti-inflammatory cytokine IL-13 (IL-13Mφs), which increase intraspinal alternatively activated Mφ numbers following transplantation in SCI mice, creating a perilesional environment prone to functional regeneration. We hypothesize that these IL-13Mφs suppress premature immune-aging. In addition, IL-13Mφs may enhance functional recovery of SCI in aged mice. Finally, we will translate these results to the situation in humans, by testing the findings in an immune and neuronal cell co-culture system derived from human induced pluripotent stem cells.

Period of project

01 December 2020 - 30 November 2024