Engineered T regulatory cells target CNS and suppress active EAE upon intra nasal delivery
(English)Manuscript (preprint) (Other academic)
Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS). In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, T regulatory (Treg) cell therapy has proven beneficial. However, systemic administration of such cells may immunologically compromise the recipient and promote infections due to general immunosuppression. We hypothesized that Tregs can be equipped with a CNS-targeting receptor and be delivered intra-nasally to avoid systemic exposure. In the current investigation, CD4+ T cells were modified with a lentiviral vector system to express a myelin oligodendrocyte (MOG)-targeting receptor in trans with the FoxP3 gene that drives Treg differentiation. The genetically engineered Tregs demonstrated suppressive capacity in vitro and were then tested in the EAE model. Engineered Tregs localized to the brain and suppressed ongoing encephalomyelitis in vivo. Cured mice were rechallenged with an EAE-inducing inoculum but remained healthy. Cytokine profile of the brain reveled lower levels of effector cytokines in TregCAR treated mice and acordingly, reduced axonal damage was seen in these mice. In conclusion, CNS-specific Tregs were able to localize to the CNS and efficiently cure mice with ongoing EAE.
Treg EAE CAR Targeting CNS
Immunology in the medical area
Research subject Medicine
IdentifiersURN: urn:nbn:se:uu:diva-132738OAI: oai:DiVA.org:uu-132738DiVA: diva2:359059