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Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities
Brian J. Nickoloff, Frank O. Nestle
Brian J. Nickoloff, Frank O. Nestle
Published June 15, 2004
Citation Information: J Clin Invest. 2004;113(12):1664-1675. https://doi.org/10.1172/JCI22147.
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Science in Medicine

Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities

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Abstract

Chronic and excessive inflammation in skin and joints causes significant morbidity in psoriasis patients. As a prevalent T lymphocyte–mediated disorder, psoriasis, as well as the side effects associated with its treatment, affects patients globally. In this review, recent progress is discussed in the areas of genetics, the immunological synapse, the untangling of the cytokine web and signaling pathways, xenotransplantation models, and the growing use of selectively targeted therapies. Since psoriasis is currently incurable, new management strategies are proposed to replace previous serendipitous approaches. Such strategic transition from serendipity to the use of novel selective agents aimed at defined targets in psoriatic lesions is moving rapidly from research benches to the bedsides of patients with this chronic and debilitating disease.

Authors

Brian J. Nickoloff, Frank O. Nestle

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Figure 4

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Immune synapse_related signaling pathway and autoimmune diseases. A poss...
Immune synapse_related signaling pathway and autoimmune diseases. A possible role for genetic mutations involved in several autoimmune diseases is highlighted, including ZAP-70 (RA); SLC9A3R1 and NAT9 (psoriasis); PDCD1 (systemic lupus erythematosus [SLE]); and SLC22A4 (RA and Crohn disease). T lymphocytes contain both surface receptors and intracellular signaling components that become activated when the TCR is engaged by interactions with an appropriate APC in which antigen is presented in the context of MHC molecules. The APC is displayed in the upper portion of this schematic view. The TCR mediates signaling in conjunction with molecules located in the plasma membrane, including CD3 and ζ-chains, which contribute to the formation of an immunological synapse and a lipid raft, leading to activation of proximal, intermediate, and distal signaling components. Several but not all components are portrayed in this figure. Ultimately, transcription factors become activated and bind to respective promoter regions to either enhance or suppress target gene expression. Potential mechanisms linking the genetic findings to functional components of the immunological synapse are shown by solid bold lines.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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