Pattern recognition receptors in immune disorders affecting the skin.

Contains fulltext : 109004.pdf (publisher's version ) (Open Access)Pattern recognition receptors (PRRs) evolved to protect organisms against pathogens, but excessive signaling can induce immune responses that are harmful to the host. Putative PRR dysfunction is associated with numerous immune disorders that affect the skin, such as systemic lupus erythematosus, cryopyrin-associated periodic syndrome, and primary inflammatory skin diseases including psoriasis and atopic dermatitis. As yet, the evidence is often confined to genetic association studies without additional proof of a causal relationship. However, insight into the role of PRRs in the pathophysiology of some disorders has already resulted in new therapeutic approaches based on immunomodulation of PRRs

3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells

Different pharmacologically active components have been isolated from royal jelly. Some of them possess imunomodulatory activity, but the mechanisms of their effect on the immune system have not been elucidated yet. In this study we tested the effect of 3,10-dihydroxy-decanoic acid (3,10-DDA), a fatty acid isolated from royal jelly, on maturation and functions of human monocyte-derived dendritic cells (MoDCs). We showed that 3,10-DDA stimulated maturation of MoDCs by up-regulating the expression of CD40, CD54, CD86 and CD1a, and increased their allostimulatory potential in co-culture with allogeneic CD4+T cells. 3,10-DDA-treated MoDCs enhanced the production of IL-12 and IL-18, and stimulated the production of interferon-γ in co-culture with allogeneic CD4+T cells, compared to control MoDCs. In contrast, the production of IL-10 was down-regulated. In conclusion, our results suggest that 3,10-DDA stimulates maturation and Th1 polarising capability of human MoDCs in vitro, which could be beneficial for anti-tumour and anti-viral immune responses. © 2010 Elsevier Ltd. All rights reserved

Monitoring the Initiation and Kinetics of Human Dendritic Cell-Induced Polarization of Autologous Naive CD4⁺ T Cells

<div><p>A crucial step in generating <i>de novo</i> immune responses is the polarization of naive cognate CD4⁺ T cells by pathogen-triggered dendritic cells (DC). In the human setting, standardized DC-dependent systems are lacking to study molecular events during the initiation of a naive CD4⁺ T cell response. We developed a TCR-restricted assay to compare different pathogen-triggered human DC for their capacities to instruct functional differentiation of autologous, naive CD4⁺ T cells. We demonstrated that this methodology can be applied to compare differently matured DC in terms of kinetics, direction, and magnitude of the naive CD4⁺ T cell response. Furthermore, we showed the applicability of this assay to study the T cell polarizing capacity of low-frequency blood-derived DC populations directly isolated <i>ex vivo</i>. This methodology for addressing APC-dependent instruction of naive CD4⁺ T cells in a human autologous setting will provide researchers with a valuable tool to gain more insight into molecular mechanisms occurring in the early phase of T cell polarization. In addition, it may also allow the study of pharmacological agents on DC-dependent T cell polarization in the human system.</p></div