IL-17A production in human psoriatic blood and lesions by CD146+ T Cells

CD146, also called melanoma cell adhesion molecule (MCAM), is a cell surface adhesion molecule on endothelial cells involved in homotypic and heterotypic cell interactions (Bardin et al, 2001). CD146 binding in endothelial cells (ECs) leads to a change in cellular permeability, actin distribution and redistribution of NF-kappa B p50 to the nucleus. CD146 has been shown to be present on 1–3% of circulating peripheral blood T cells in healthy humans (Elshal et al, 2005). CD146+ T cells have an effector memory phenotype, demonstrate up-regulation of a cluster of genes involved with adhesion, migration, homing, and inflammation, and have enhanced binding to endothelial monolayers in vitro (Elshal et al, 2007). These features of the CD146+ T cells in the peripheral circulation have led to speculation that these represent a small pool of cells primed for extravasation and/or homing of activated T cells (Elshal et al, 2007, Guezguez et al, 2007) in response to inflammatory stimuli. Circulating CD146+ T cells are elevated in several inflammatory autoimmune diseases such as sarcoidosis, inflammatory bowel disease, multiple sclerosis, connective tissue disease, and Behcet's disease and produce IL-17 (Dagur et al, 2011, Dagur et al, 2010, LaRochelle et al, 2012). Whether these cells play a role at the site of active inflammation in