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

Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. Methodology and Principal Findings: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16. F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B-and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clini

Immune-related antigens, surface molecules and regulatory factors in human-derived mesenchymal stromal cells: the expression and impact of inflammatory priming.

Based on their ability to regulate immune responses, MSCs are considered to be potential candidates for managing immune-mediated diseases in the context of immune therapy. AT and WJ are considered valuable alternatives for BM as a source of MSCs. A detailed and comparative characterization of the immunological profile of MSCs derived from different sources, as well as an understanding of their responsiveness under certain circumstances, such as inflammation, is required to facilitate efficient and well-designed clinical studies. Flow cytometric analyses revealed clear differences among MSC types concerning the expression of the endothelial (e.g. CD31, CD34, CD144 and CD309) and stromal (e.g. CD90 and CD105) associated markers. Regardless of their source, MSCs did not express any of the known hematopoietic markers. All MSCs were uniformly positive for HLA-ABC and lacked the expression of HLA-DR and the co-stimulatory molecules (e.g. CD40, CD80, CD86, CD134 and CD252) required for full T-cell activation. Tissue-specific MSCs presented a modulated expression of cell adhesion molecules that is important for their cellular interactions. MSCs exhibited several surface (e.g. CD73, HLA-G, HO-1 and CD274) and soluble (e.g. HGF, PGE2 and IGFBP-3) immunoregulatory molecules. According to these immunological profiles, the present work provides evidence that the source from which MSCs are derived is important for the design of MSC-based immunointervention approaches. In light of these observations, we may suggest that WJ-MSCs appear to be the most attractive cell population to use in immune cellular therapy when immunosuppressive action is required.Clinical TrialJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe