Abstract
Loss-function mutations in the Activity-dependent neuroprotective protein (ADNP) gene have been
linked to the Helsmoortel-Van der Aa Syndrome, a complex neurological disorder characterized by
autism and intellectual disability. The Adnp mutant mice recapitulate key hallmark of autism
spectrum disorders including learning deficit, increased anxiety and repetitive behavior. ADNP is
involved in brain development and neuroprotection. In addition to the neuroprotective effect, ADNP
also has immunomodulatory effects. ADNP is expressed in cells of the immune system and can
suppress the production of pro-inflammatory cytokines. Studies in Multiple Sclerosis have linked
ADNP deficiency to reduced regulatory T cell function, an immunomodulatory subset of T cells. A
better understanding of the immune changes associated with ADNP deficiency may provide clues to
pathological processes and allow to identify biological markers that enable early diagnosis and
treatment of ASD. In this project, we will explore the role of ADNP in T cells function, to this end will
perform in depth characterization of the molecular and cellular signature acquired by T cells and
microglia cell populations in the mutant mice. We hypothesize that in Adpn mice defective function of
Regulatory T cells exacerbate the pathology. We will use a tailored gene therapy to specifically
expand Regulatory T cells in the brain and evaluate the effect on the behaviour of the Adpn mutant
mice
Researcher(s)
Research team(s)
- VIB CMN - Neuroimmunology
Project type(s)