Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities.

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.

SUBMITTER: Nickoloff BJ

PROVIDER: S-EPMC420513 | biostudies-literature | 2004 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities.

Nickoloff Brian J BJ Nestle Frank O FO

The Journal of clinical investigation 20040601 12

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 psor ...[more]

PMID: 15199399

Similar Datasets

Functional roles of SRC signaling in pancreatic cancer: Recent insights provide novel therapeutic opportunities.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease with a 5-year survival rate of <10%. Aberrant activation or elevated expression of the tyrosine kinase c-SRC (SRC) is frequently observed in PDAC and is associated with a poor prognosis. Preclinical studies have revealed a multifaceted role for SRC activation in PDAC, including promoting chronic inflammation, tumor cell proliferation and survival, cancer cell stemness, desmoplasia, hypoxia, angiogenesis, invasion, metastasis, and drug resistance. Strategies to inhibit SRC signaling include suppressing its catalytic activity, inhibiting protein stability, or by interfering with signaling components of the SRC signaling pathway including suppressing protein interactions of SRC. In this review, we discuss the molecular and immunological mechanisms by which aberrant SRC activity promotes PDAC tumorigenesis. We also provide a comprehensive update of SRC inhibitors in the clinic, and discuss the clinical challenges associated with targeting SRC in pancreatic cancer.

| S-EPMC10238273 | biostudies-literature

Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis.

Project description:Psoriasis is a common, immunologically mediated, inflammatory and hyperproliferative disease of the skin and joints, with a multifactorial genetic basis. We earlier mapped PSORS1, the major psoriasis susceptibility gene in the major histocompatibility complex (MHC), to within or very near HLA-Cw6. In an effort to identify non-MHC psoriasis genes, we carried out a collaborative genome-wide association study. After the initial follow-up genotyping of 21 single nucleotide polymorphisms from 18 loci, showing strong evidence of association in the initial scan, we confirmed evidence of association at seven loci. Three of these loci confirm earlier reports of association (HLA-C, IL12B, IL23R) and four identify novel signals located near plausible candidate genes (IL23A, IL4/IL13, TNFAIP3 and TNIP1). In other work, we have also shown that interferon-gamma (IFN-gamma) treatment induces interleukin (IL)-23 mRNA and protein in antigen-presenting cells (APC), leading to the proliferation of CD4+ and CD8+ memory T cells expressing IL-17. Although functional variants remain to be identified, we speculate that genetic variants at the IL4/IL13 locus contribute to the Th1 bias that is characteristic of psoriasis, that Th1-derived IFN-gamma supports expansion of IL-17+ T cells through APC-derived IL-23 and that negative regulation of inflammatory signaling through the NF-kappaB axis is impaired because of genetic variants of TNFAIP3 and TNIP1.

| S-EPMC2683580 | biostudies-literature

TRP Channels and Migraine: Recent Developments and New Therapeutic Opportunities.

Project description:Migraine is the second-most disabling disease worldwide, and the second most common neurological disorder. Attacks can last many hours or days, and consist of multiple symptoms including headache, nausea, vomiting, hypersensitivity to stimuli such as light and sound, and in some cases, an aura is present. Mechanisms contributing to migraine are still poorly understood. However, transient receptor potential (TRP) channels have been repeatedly linked to the disorder, including TRPV1, TRPV4, TRPM8, and TRPA1, based on their activation by pathological stimuli related to attacks, or their modulation by drugs/natural products known to be efficacious for migraine. This review will provide a brief overview of migraine, including current therapeutics and the link to calcitonin gene-related peptide (CGRP), a neuropeptide strongly implicated in migraine pathophysiology. Discussion will then focus on recent developments in preclinical and clinical studies that implicate TRP channels in migraine pathophysiology or in the efficacy of therapeutics. Given the use of onabotulinum toxin A (BoNTA) to treat chronic migraine, and its poorly understood mechanism, this review will also cover possible contributions of TRP channels to BoNTA efficacy. Discussion will conclude with remaining questions that require future work to more fully evaluate TRP channels as novel therapeutic targets for migraine.

| S-EPMC6631099 | biostudies-literature

Involvement of PDGF in fibrosis and scleroderma: recent insights from animal models and potential therapeutic opportunities.

Project description:Fibrosis is the principal characteristic of the autoimmune disease known as scleroderma or systemic sclerosis (SSc). Studies published within the last three years suggest central involvement of platelet-derived growth factors (PDGFs) in SSc-associated fibrosis. PDGFs may also be involved in SSc-associated autoimmunity and vasculopathy. The PDGF signaling pathway is well understood and PDGF receptors are expressed on collagen-secreting fibroblasts and on mesenchymal stem and/or progenitor cells that may affect SSc in profound and unexpected ways. Although much work remains before we fully understand how PDGFs are involved in SSc, there is much interest in using PDGF inhibitors as a therapeutic approach to SSc.

| S-EPMC5570472 | biostudies-other

Acquired and congenital forms of heterotopic ossification: new pathogenic insights and therapeutic opportunities.

Project description:Heterotopic ossification (HO) involves the formation and accumulation of extraskeletal bone tissue at the expense of local tissues including muscles and connective tissues. There are common forms of HO that are triggered by extensive trauma, burns and other bodily insults, and there are also rare congenital severe forms of HO that occur in children with Fibrodysplasia Ossificans Progressiva or Progressive Osseous Heteroplasia. Given that HO is often preceded by inflammation, current treatments usually involve anti-inflammatory drugs alone or in combination with local irradiation, but are not very effective. Recent studies have provided novel insights into the pathogenesis of acquired and genetic forms of HO and have used the information to conceive and test new and more specific therapies in animal models. In this review, I provide salient examples of these exciting and promising advances that are undoubtedly paving the way toward resolution of this debilitating and at times fatal disease.

| S-EPMC6015534 | biostudies-literature

Model organoids provide new research opportunities for ductal pancreatic cancer.

Project description:We recently established organoid models from normal and neoplastic murine and human pancreas tissues. These organoids exhibit ductal- and disease stage-specific characteristics and, after orthotopic transplantation, recapitulate the full spectrum of tumor progression. Pancreatic organoid technology provides a novel platform for the study of tumor biology and the discovery of potential biomarkers, therapeutics, and personalized medicine strategies.

| S-EPMC4845167 | biostudies-other

Key Signaling Pathways in Psoriasis: Recent Insights from Antipsoriatic Therapeutics.

Project description:Psoriasis is a common chronic inflammatory skin disease associated with several comorbidities and reduced quality of life. In the past decades, highly effective targeted therapies have led to breakthroughs in the management of psoriasis, providing important insights into the pathogenesis. This article reviews the current concepts of the pathophysiological pathways and the recent progress in antipsoriatic therapeutics, highlighting key targets, signaling pathways and clinical effects in psoriasis.

| S-EPMC8254604 | biostudies-literature

Structure of a Potential Therapeutic Antibody Bound to Interleukin-16 (IL-16): MECHANISTIC INSIGHTS AND NEW THERAPEUTIC OPPORTUNITIES.

Project description:Interleukin-16 (IL-16) is reported to be a chemoattractant cytokine and modulator of T-cell activation, and has been proposed as a ligand for the co-receptor CD4. The secreted active form of IL-16 has been detected at sites of TH1-mediated inflammation, such as those seen in autoimmune diseases, ischemic reperfusion injury (IRI), and tissue transplant rejection. Neutralization of IL-16 recruitment to its receptor, using an anti-IL16 antibody, has been shown to significantly attenuate inflammation and disease pathology in IRI, as well as in some autoimmune diseases. The 14.1 antibody is a monoclonal anti-IL-16 antibody, which when incubated with CD4(+) cells is reported to cause a reduction in the TH1-type inflammatory response. Secreted IL-16 contains a characteristic PDZ domain. PDZ domains are typically characterized by a defined globular structure, along with a peptide-binding site located in a groove between the ?B and ?B structural elements and a highly conserved carboxylate-binding loop. In contrast to other reported PDZ domains, the solution structure previously reported for IL-16 reveals a tryptophan residue obscuring the recognition groove. We have solved the structure of the 14.1Fab fragment in complex with IL-16, revealing that binding of the antibody requires a conformational change in the IL-16 PDZ domain. This involves the rotation of the ?B-helix, accompanied movement of the peptide groove obscuring tryptophan residue, and consequent opening up of the binding site for interaction. Our study reveals a surprising mechanism of action for the antibody and identifies new opportunities for the development of IL-16-targeted therapeutics, including small molecules that mimic the interaction of the antibody.

| S-EPMC4974395 | biostudies-literature

ATM-Deficient Cancers Provide New Opportunities for Precision Oncology.

Project description:Poly-ADP ribose polymerase (PARP) inhibitors are currently used in the treatment of several cancers carrying mutations in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2, with many more potential applications under study and in clinical trials. Here, we discuss the potential for extending PARP inhibitor therapies to tumours with deficiencies in the DNA damage-activated protein kinase, Ataxia-Telangiectasia Mutated (ATM). We highlight our recent findings that PARP inhibition alone is cytostatic but not cytotoxic in ATM-deficient cancer cells and that the combination of a PARP inhibitor with an ATR (ATM, Rad3-related) inhibitor is required to induce cell death.

| S-EPMC7140103 | biostudies-literature