Obiettivo
Multiple sclerosis (MS) is an autoimmune disease whose pathology is directly mediated by inflammatory autoimmune T cells. The mechanisms determining the initiation of inflammation by T cells are still unknown. Since antigen presenting cells (APC) play a crucial role in the activation of T cells, their involvement in directing the quality of T cell responses in MS is likely. Thelper (Th) 17 type of immune response is responsible for mediating pathogenesis during autoimmunity. In contrast, Tregulatory (Treg) cells suppress the functions of effector T cells, thereby protecting tissues from the devastating damage inflicted by non-specific inflammation. A delicate balance of soluble factors is involved in the differentiation of naïve T cells into either polarized inflammatory Th17 or suppressive Treg cells. Moreover, the increase of Th17/Treg ratio in MS patients suggests a functional antagonism between Th17 and Treg cells, and a dichotomy in their generation as well. In this project we aim to characterize the involvement of APC in the Th17/Treg balance during MS disease. We will purify primary APC subsets and we will stimulate them ex vivo with Toll like receptor (TLR) agonists. A specific transcriptional profile of APC purified from MS patients versus healthy donors will permit to select genes differentially expressed and potentially involved in the activation of T cells. In order to clarify the role of selected APC molecules, we will block them before coculture APC with naïve/memory T cells. Differentiation of T cells will be analysed through the measurement of Th17- and Treg-specific features and in vitro functional assays. These results will clarify whether the signals originating from APC in MS patients underlie the Th17/Treg imbalance. Moreover, the characterization of molecular mechanisms adopted by APC in controlling T cell response in MS disease, will be important to pharmacologically influence the immunity towards an anti-inflammatory response in MS patients.
Campo scientifico
Invito a presentare proposte
FP7-PEOPLE-2009-RG
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Meccanismo di finanziamento
MC-ERG - European Re-integration Grants (ERG)Coordinatore
00179 Roma
Italia