Immuno-pathogenesis Sample Clauses

Immuno-pathogenesis. Psoriatic skin inflammation is determined by a crosstalk between keratinocytes and cells of the adaptive and innate immune system. Seminal work carried out on a xeno- trasplantation model of the disease demonstrated that self-DNA and self-RNA can both form complexes with the LL-37 cationic peptide and recruit plasmacytoid dendritic cells (pDCs) to pre-psoriatic skin. The release of IFN-α by activated pDC is a key early event in the pathogenesis of psoriasis, as this cytokine can promote the migration of dermal dendritic cells (DDCs) to skin-draining lymph nodes, where DDC can trigger the differentiation of naïve T-cells into Th1 and Th17 lymphocytes (Xxxxxx, Xxxxxx et al. 2005; Xxxxx, Xxxxxxxx et al. 2007). DDCs and inflammatory DCs also secrete IL-12, IL- 20, IL-23, TNF-α and nitric oxide (NO), which cause resident immune cells to produce more pro-inflammatory cytokines. Thus, increased levels of IFN-γ, TNF-α, IL-17 and IL- 22 sustain the activation of keratinocytes, which produce more chemokines (thereby promoting the recruitment of further inflammatory cells) and more LL-37 (leading to the release of further IFN-α). These events drive an amplified inflammatory reaction which ultimately results in the formation of a psoriatic plaque (Figure 1.1. 2.1) (Xxx, Xx Xxxxxx et al. 2011). Figure 1.1.2.1 Overview of the events leading to the formation of a psoriatic plaque. Disease onset is determined by a combination of environmental triggers and inherited susceptibility alleles. Following skin injury or trauma, keratinocytes release pro- inflammatory cytokines (TNF-α, IL-6 and IL-1β) as well as self DNA and/or RNA. The latter can form complexes with LL-37 and ultimately promote the differentiation of Th1 and Th17 lymphocytes, via the activation of pDCs and DDCs. Adapted from (Xxx, Xx Xxxxxx et al. 2011)