Psoriasis and Down syndrome: a report of three cases and a potential pathophysiologic link.

Psoriasis is thought to result from an influx of Th1 and Th17 cells driven by the production of cytokines such as interferon (IFN)-gamma, IL-2, and tumor necrosis factor (TNF)-alpha elicited by skin immunocytes. We report three cases of patients with chronic plaque psoriasis and concomitant Down syndrome. Although there is no direct link between Down syndrome and the Th17 pathway, there are data supporting a dysregulation of the IFN system in this patient population.

Caveolin-1 expression determines the route of neutrophil extravasation through skin microvasculature.

Interleukin-8 plays a key role in the acute inflammatory response by mediating recruitment of neutrophils through vessel walls into affected tissues. During this process, molecular signals guide circulating blood neutrophils to target specific vessels for extravasation and to migrate through such vessels via particular routes. Our results show that levels of endothelial caveolin-1, the protein responsible for the induction of the membrane domains known as caveolae, are critical to each of these processes.

Transcellular migration of neutrophils is a quantitatively significant pathway across dermal microvascular endothelial cells.

Neutrophil extravasation is central to inflammatory skin diseases like psoriasis and atopic dermatitis. In vivo, neutrophils have been shown to migrate through cell-to-cell junctions (paracellular pathway) or directly through the body of the endothelial cell (transcellular pathway). In vitro, however, neutrophil migration is a largely paracellular process where cells preferentially cross at tricellular corners devoid of tight junctions.

Balancing immunity and immunosuppression: vaccinating patients receiving treatment with efalizumab.

Although effective in the treatment of immunodysregulatory diseases such as psoriasis, targeted immunosuppressive agents may confer risks of both enhanced susceptibility to infection and decreased responsiveness to vaccination. In a recent study, Krueger et al. (this issue) investigated these issues by testing the immune response to both a model antigen and a therapeutic vaccination in psoriasis patients during and after treatment with an LFA-1 inhibitor, efalizumab.

Tyrosine phosphorylation of caveolin-2 at residue 27: differences in the spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27).

Caveolin-2 is an accessory molecule and the binding partner of caveolin-1. Previously, we showed that c-Src expression leads to the tyrosine phosphorylation of Cav-2 at position 19. To further investigate the tyrosine phosphorylation of Cav-2, we have now generated a novel phospho-specific antibody directed against phospho-Cav-2 (pY27).

An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells.

Lymphoid tissue inducer (LTi) cells are associated with early development of lymph nodes and Peyer's patches. We show here that during fetal life the nuclear hormone receptor RORgamma(t) is expressed exclusively in and is required for the generation of LTi cells. RORgamma(t+) LTi cells provide essential factors, among which lymphotoxin-alpha1beta2 is necessary but not sufficient for activation of the mesenchyma in lymph node and Peyer's patch anlagen.