Fare Modelinde T-Reg Kaynaklı Eksozomların Multiple Skleroz Ve Psoriazisde Önleyici Ve Tedavi Edici Etkilerinin Araştırılması

TÜBİTAK Uluslararası Çoklu İşbirliği Projesi , 2021 - 2023

Adoptive Treg cell transfer has emerged as a treatment modality in autoimmune diseases, however, the

issues regarding the instability/and plasticity of ex vivo expanded Treg cells following transfer into patients

have surfaced as one of the disadvantages of such therapy. Thus, there is a need for improved Treg cell

therapies. Treg cells have been shown to suppress T and other immune cells at least in part through

exosome mediated mechanisms. In this project we aim to test the therapeutic potential of cell-free Treg cellderived

exosomes in the treatment of two distinct autoimmune diseases whose pathogenesis have been

shown to be mediated by TH17 cells. In the first model, exosomes will be delivered systemically, in the latter

locally (topically and intradermally). Therapeutic potential of systemically delivered exosomes will be tested

in a multiple sclerosis mouse model Induced by MOG35-55 immunization. Exosomes will be given to mice

before and after the onset of the disease to test the preventative and therapeutic impact of Treg cell-derived

exosomes. The disease development will be monitored by scoring EAE, quantifying demyelination in the

brain/spinal cord and characterizing immune cell response in the lymph node during priming and in the

central nervous system at the peak of the disease. To test the therapeutic potential of locally delivered Tregderived

exosomes, psoriasis model will be developed by topical application of imiquimod in C57BL/6 mice.

Skin pathology will be assessed by histological staining and measuring dermal thickness, as well as

quantification of inflammatory cytokines by real time qPCR or of CD4+ T cells subsets by flow cytometry. The

use of Treg derived cell-free exosomes has so far only been tested in a transplant model. Therefore, the

proposed project will be a proof of concept for use of exosomes in this regard and will allow us to apply this

therapy to two distinct autoimmune disease settings as systemic and topical applications.