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Getting Under the Skin: Targeting Cutaneous Autoimmune Disease.

ABSTRACT: Autoimmune diseases of the skin occur when the immune system attacks normal skin. The immune system can be broadly divided into an effector arm responsible for fighting infections and cancer and a regulatory arm that reduces autoreactivity and maintains immune homeostasis. Cutaneous autoimmunity develops when the equilibrium between the effector arm and regulatory arm of the immune system is disrupted. Recent insights into the inflammatory pathways that are overactive in some cutaneous autoimmune diseases have led to therapies targeting the effector arm of the immune system with greater treatment efficacy than previously used broad immunosuppressants. The current paradigm of inhibiting excessive immune activation for treating cutaneous autoimmunity will be discussed including cytokine blockade, cellular depletion, intracellular signaling blockade and costimulatory blockade. Despite the success of this approach many cutaneous autoimmune diseases lack a clearly delineated pathway to target and therefore new strategies are needed. An emerging therapeutic strategy targeting the regulatory arm of the immune system to induce tolerance and disease remission provides new hope for treating cutaneous autoimmunity. Such an approach includes cellular therapy with regulatory T cells and chimeric autoantibody receptor T cells, cytokine therapy with low-dose interleukin-2, immune checkpoint stimulation, tolerogenic vaccines and microbiome biotherapy. This mini-review will discuss the current and emerging therapeutic strategies for cutaneous autoimmune diseases and provide an organizational framework for understanding distinct mechanisms of action.

SUBMITTER: Vesely MD

PROVIDER: S-EPMC7087062 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Getting Under the Skin: Targeting Cutaneous Autoimmune Disease.

Vesely Matthew D MD

The Yale journal of biology and medicine 20200327 1

Autoimmune diseases of the skin occur when the immune system attacks normal skin. The immune system can be broadly divided into an effector arm responsible for fighting infections and cancer and a regulatory arm that reduces autoreactivity and maintains immune homeostasis. Cutaneous autoimmunity develops when the equilibrium between the effector arm and regulatory arm of the immune system is disrupted. Recent insights into the inflammatory pathways that are overactive in some cutaneous autoimmun ...[more]

PMID: 32226348

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Project description:BackgroundVideo stimulated recall (VSR) is a method of enhancing participants' accounts of the consultation using a video recording of the event to encourage and prompt recall in a post consultation interview. VSR is used in education and education research, and to a lesser extent in medical and nursing research. Little is known about the sort of research questions that lend themselves best to the use of VSR or the impact of the specific VSR procedure on study quality. This systematic review describes studies in primary care that have used the method and aims to identify the strengths, weaknesses and role of VSR.MethodsA systematic literature search has been conducted to identify primary care consultation research using VSR. Two authors undertook data extraction and quality appraisal of identified papers and a narrative synthesis has been conducted to draw together the findings. In addition, theory on classifying VSR procedures derived from other disciplines is used as a lens through which to assess the relevance of VSR technique.ResultsTwenty eight publications were identified that reported VSR in primary care doctor-patient consultation research. VSR was identified as a useful method to explore specific events within the consultation, mundane or routine occurrences, non-spoken events and appears to particularly add value to doctor's post consultation accounts. However, studies frequently had insufficient description of methods to properly evaluate both the quality of the study, and the influence of VSR technique on findings.ConclusionsVSR is particularly useful for study of specific consultation events when a 'within case' approach is used in analysis, comparing and contrasting findings from the consultation and post-consultation interview. Alignment of the choice of VSR procedure and sampling to the study research question was established as particularly important in the quality of studies. Future researchers may consider the role of process evaluation to understand further the impact of research design on data yielded and the acceptability of the method to participants.

Project description:MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that control genes at post-transcriptional level. They are essential for development and tissue differentiation, and altered miRNA expression patterns are linked to the pathogenesis of inflammation and cancer. There is evidence that miRNA expression is genetically controlled similar to the transcription of protein-coding genes and previous studies identified quantitative trait loci (QTL) for miRNA expression in the liver. So far, little attention has been paid to miRNA expression in the skin. Moreover, there is no data on epistatic control of miRNA expression. In this study, we statistically linked cutaneous miRNA expression patterns to SNP (single nucleotide polymorphism) markers in an advanced murine intercross line (AIL) of three strains (BxD2, NZM and MRL) that are known to be prone to develop autoimmune diseases as well as the wild-derived strain CAST/EiJ. In particular, we screened 100 murine samples for 609 different miRNAs and identified 42 eQTL controlling the expression of 38 cutaneous miRNAs. As a result, we identified two chromosomal hot-spots on chromosome 2 and 8 that control the expression of multiple miRNAs. Moreover, for eight miRNAs, an interacting effect of pairs of SNP was observed. Combining the constraints on genes from the statistical interaction of their loci and further using curated protein interaction networks narrowed down the number of candidate genes controlling miRNAs to a set of several genes. Among the resulting interaction pairs were the genes COMMD3 and COPS5 found to regulate the expression of miR-501-5p. Independently, a network analysis based on co-expression of miRNAs was performed using WGCNA (weighted gene co-expression analysis) to identify clusters (modules) of co-expressed miRNAs. One of these modules significantly correlated with the onset and severity of epidermolysis bullosa acquisita, a cutaneous autoimmune skin blistering disease induced by autoantibodies to type VII collagen. The key miRNAs identified from this analysis were miR-379 and miR-223.This work shows strong evidence for a genetic control of cutaneous miRNA expression. 100 murine skin samples

Dataset Information

Getting Under the Skin: Targeting Cutaneous Autoimmune Disease.

Publications

Getting Under the Skin: Targeting Cutaneous Autoimmune Disease.

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