Psoriasis is one of the most common human skin diseases and is considered to have key genetic underpinnings. It is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells, dendritic cells and various immune-related cytokines and chemokines implicated in pathogenesis. The newest therapies for psoriasis target its immune components and may predict potential treatments for other inflammatory human diseases.

Pathogenesis and therapy of psoriasis

The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-γ, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The assoc...

Immunology of Psoriasis

Psoriasis is one of the most common T cell-mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-alpha-producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-alpha early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-alpha signaling or inhibiting the ability of PDCs to produce IFN-alpha prevented the T cell-dependent development of psoriasis. Furthermore, IFN-alpha reconstitution experiments demonstrated that PDC-derived IFN-alpha is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-alpha represent potential early targets for the treatment of psoriasis.

https://rupress.org/jem/article-pdf/202/1/135/1399027/jem2021135.pdf

Plasmacytoid predendritic cells initiate psoriasis through interferon-α production

The IL-23/Th17 Axis in the Immunopathogenesis of Psoriasis

Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells.

Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and ‘Type 1’ inflammatory gene expression

Current concepts in the immunopathogenesis of psoriasis.

Summary

Background Behcet’s disease (BD) is a multisystemic chronic inflammatory disease with unknown aetiology. Interleukin (IL)-12, which is involved in the pathogenesis of BD, is a 70-kDa cytokine made of p35 and p40 subunits. Recently, IL-23, which is composed of a p19 subunit and a shared p40 subunit of IL-12, was discovered; as a consequence, this raises the need to re-examine previous IL-12 reports to determine whether IL-23 is also involved in BD pathogenesis.



Objectives  To determine whether there are changes in IL-23 in skin lesions and sera of patients with BD.



Methods  For quantitative reverse transcription–polymerase chain reaction, the total cellular RNA of erythema nodosum (EN)-like skin lesions from patients with BD, psoriasis skin lesions and skin biopsy samples from normal individuals was analysed. To determine cytokine levels, sera from patients with BD and normal individuals were analysed.



Results  Increased IL-23 p19 mRNA levels were observed for both EN-like lesions of patients with BD and skin lesions of patients with psoriasis compared with normal individuals. Although we observed an elevation of IL-12/23 p40 mRNA expression in the BD lesions, this was not significant. Moreover, the levels of IL-12 p35 mRNA in BD lesions were also not significantly different from the levels in normal control skin. In addition, no significant changes were detected in serum IL-12 and IL-23 levels between patients with BD and normal control individuals, or in patients with BD before and after treatment.



Conclusions  Increased expression of IL-23 p19 mRNA in BD lesions suggests that IL-23 may be associated with the development of the EN-like lesions in patients with active BD.

Increased expression of interleukin-23 p19 mRNA in erythema nodosum-like lesions of Behçet's disease.

Nail changes are common side effects of taxane chemotherapeutic agents. Docetaxel (Taxotere) is known to cause a great incidence of nail change. Various types of nail changes have previously been reported as a result of treatment with taxanes. We describe 2 cases of severe nail changes induced by docetaxel. The patients had previously been diagnosed with breast cancer and advanced gastric cancer, respectively. During the course of treatment with docetaxel, nail changes became apparent in both patients. Initially, they complained of nail bed purpura. Subungual hematomas with hemopurulent discharge were later observed in several fingers. Drainage of the hemopurulent material occurred spontaneously in our cases, leading to onycholysis. Following drainage, the pain in the nail with subungual hemoprulent material was relieved immediately and spontaneous healing of the patients' nails was noticed after few months. Subungual hemorrhage and suppuration therefore are considered causes of onycholysis and the pain in these patients. Although systemic or topical antibiotics were not used to treat these patients, antibiotics may be also worthwhile to hasten the drainage of the subungual hematomas and suppuration in patients for quick relief of pain.

https://synapse.koreamed.org/upload/SynapseData/PDFData/0069ymj/ymj-48-124.pdf

Docetaxel-induced onycholysis: the role of subungual hemorrhage and suppuration.

Background A difference of the interleukin-18 (IL-18) mRNA expression among several proinflammatory genes was previously observed between large plaque (LP) psoriasis patients (more than 5 cm lesions are typical) and small plaque (SP) psoriasis patients (1~2 cm lesions are typical). Therefore, it is necessary to test whether there is any difference in the expression of the genes that activate IL-18 or the expression of genes that are induced by IL-18. Objective To test the differential mRNA expressions of caspase-1, STAT-6, MMP-1, MMP-2, MMP-9 and TIMP-1 according to the clinical types of psoriasis vulgaris lesions in Korean patients, we have analyzed the skin samples of psoriasis vulgaris patients. Methods The total cellular RNA of skin samples from groups of patient with LP and SP psoriasis was analyzed by performing real-time PCR (the Taqman method) to compare the differences in the mRNA expressions. Results The caspase-1 and STAT-6 mRNA expression levels from the SP lesional skin of the patients were increased compared with the caspase-1 and STAT-6 mRNA expression levels from SP non-lesional skin or normal skin, but these expression levels from the SP non-lesional skin were not significantly different from those of the LP non-lesional skin. Among MMP-1, MMP-2, MMP-9 and TIMP-1, the expressions of MMP-1, MMP-2 and MMP-9 mRNA were increased in the SP lesional skin compared with those of the SP non-lesional skin. The MMP-1 mRNA expressions in both the LP and SP lesional skin were increased compared with those in the normal skin (p=0.028 and p=0.007 respectively). The MMP-9 mRNA expression in the LP non-lesional skin was elevated compared with the MMP-9 mRNA expression in the SP non-lesional skin (p=0.047). The TIMP-1 mRNA expression levels from the non-lesional skin and the lesional skin of the psoriasis patients and the normal skin samples were not significantly different. Conclusion The increased expression of MMP-9 mRNA in the LP non-lesional skin compared to that of the SP non-lesional skin in the psoriatic skin suggests that the increased MMP-9 mRNA expression is related to the large size type of lesion.

Wook Lew

Papers

Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and ‘Type 1’ inflammatory gene expression

Current concepts in the immunopathogenesis of psoriasis.

Increased expression of interleukin-23 p19 mRNA in erythema nodosum-like lesions of Behçet's disease.

Docetaxel-induced onycholysis: the role of subungual hemorrhage and suppuration.

The Increased Expression of Matrix Metalloproteinase-9 Messenger RNA in the Non-lesional Skin of Patients with Large Plaque Psoriasis Vulgaris