Study of mechanisms underling the balance between .. (IMMUNO BALANCE MS)
Study of mechanisms underling the balance between inflammatory and regulatory immune response in Multiple Sclerosis
(IMMUNO BALANCE MS)
Start date: Jan 1, 2010,
End date: Dec 31, 2012
"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."
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