Showing papers in "Journal of Investigative Dermatology in 2021"

TL;DR: The clinical progress in management of advanced melanoma is reviewed and the impact of the same therapies on earlier stage disease is discussed, where the agents have shown significant promise in treating resectable but high-risk clinical scenarios.

TL;DR: In this paper, the authors discuss the plasticity of distinct dermal fibroblast phenotypes, the underestimated impact of the extracellular matrix itself, and the depletion of fibroblasts subsets on skin homeostasis and aging.

TL;DR: The evidence for inflammaging in the skin, its relationship with senescence, and how this relates to declining skin structure and function are described are described.

TL;DR: The mechanisms contributing to the accumulation of senescent cells in the skin are described and how the persistence of cellular senescence can promote impaired regenerative capacity, chronic inflammation, and tumorigenesis associated with photoaging are described.

TL;DR: In this article, the development of extrinsic skin aging as a consequence of skin exposure to specific exposomal factors, their interaction with each other, and the modification of their effects on the skin by genetic factors are discussed.

TL;DR: In this article, the authors show that fibroblasts may robustly be assigned to three major types (axes A, C), which in turn are composed of 10 major subtypes (clusters), which are denominated A1, A4, B1 and B2, and C1, C4.

TL;DR: It is shown that the TNF-α-mediated activation of NLRP3 inflammasomes in patients with psoriasis may contribute to systemic inflammation, and anti-TNF therapy normalized inflammaome function, suggesting a mechanism for the cardiovascular risk-reducing effect.

TL;DR: In this article, the authors found that both systemic and cutaneous immune responses in patients with PN are skewed toward a Th22/IL-22 profile, indicating that PN may benefit from immunomodulatory therapies directed at Th22-mediated inflammation.

TL;DR: The data indicate that psoriasis is associated with an impairment of Treg and an altered cytokine milieu, and SCFA appear to restore these alterations thereby harboring therapeutic potential for Psoriasis.

TL;DR: In this paper, the authors used high-dimensional unsupervised flow cytometry analysis to identify the major IL-23+ mononuclear phagocyte and IL-17+ T-cell subsets in psoriatic skin lesions and paves the way for a better understanding of the mode of action of drugs targeting the IL23/IL-17A pathway in psoriasis.

TL;DR: Higher skin reactivity in vivo to two MRGPRX2 drug ligands in patients with chronic spontaneous urticaria is presented and selectivity for the MRG PRX2 pathway by drug ligand was demonstrated.

TL;DR: It is reported that MRGPRX2 is indeed the dominant codeine receptor of dermal MCs and that codeine-induced refractoriness could be exploited to desensitize MRG PRX2 to prevent severe pseudo-allergic reactions.

TL;DR: This systematic review identifies and critically evaluates the mechanistic and clinical evidence of new promising therapeutic targets in hidradenitis suppurativa, suggesting a direction for future mechanistic studies in HS, including more comprehensive inflammatory endotype profiling of disease.

TL;DR: It is shown that in human wound-edge keratinocytes, the expression of miR-17,miR-18a, mi-19a,MiR-19b, and mi-20a, which all belong to the mi R-17∼92 cluster, is upregulated during wound repair, but their levels are lower in chronic ulcers than acute wounds at the proliferative phase.

TL;DR: QR-313 is developed - a clinically applicable, potent AON specifically targeting exon73 that shows direct benefit for DDEB caused by exon 73 mutations and could be used to improve the wound healing quality in RDEB and DDEb.

TL;DR: In this paper, the role of TGFβ and Eph-ephrin signaling pathways in both the aberrant fibrogenesis and angiogenesis of keloids was highlighted.

TL;DR: The epilipidome - the oxidative modifications of phospholipids - of senescent dermal fibroblasts are investigated as these molecules are among the bioactive lipids which were recently identified as SASP factors and it is found that they elicit chemokine release in non-senescent FB but also interfere with TLR2/6/CD36 signaling and phagocytic capacity in macrophages.

TL;DR: In this paper, the effect of dupilumab treatment on the dynamics of circulating skin-homing T cells, which are crucial players in the pathologic mechanism of atopic dermatitis, has been studied.

TL;DR: This review will provide a comprehensive scenario of the main phenotypical, molecular, and immunological markers related to MF pathogenesis and disease evolution, which could represent the target for the development of innovative effective treatments in this disease.

TL;DR: Using an unbiased proteomics approach, this article assessed cardiovascular-, cardiometabolic-, and inflammation-related biomarkers in the serum of patients with moderate-to-severe Hidradenitis suppurativa.

TL;DR: Domatinostat not only exerts direct anti-tumoral effects, but also restores HLA class I surface expression on MCC cells, restoring surviving MCC Cells' susceptibility to recognition and elimination by cognate cytotoxic T cells.

TL;DR: In this paper, the authors identify CYP1A1 enzymatic activity as a critical regulator of beneficial AHR signaling in the context of skin inflammation, and demonstrate that inhibition of CYP 1A1 activity ameliorated the skin immunopathology by restoring beneficial Ahr signaling.

TL;DR: In this paper, the combination of a TGFβ signaling inhibitor and immune checkpoint blockade could reverse immune evasion to reduce tumor growth, supporting cancer survival, immune evasion, and metastasis.

TL;DR: Evaluating the performance and concordance of the proposed PG diagnostic frameworks found that the three criteria agreed in their diagnoses for 72% of patients, and future research should seek to refine these diagnostic frameworks and identify targeted methods of testing, to reduce rates of PG misdiagnosis and patient misclassification in clinical trials.

TL;DR: A deeper understanding of how enzymatic changes in chromatin structure can modify the skin immune system is explained and may explain how environmental exposures during life, and the microbiome, lead to both short-term and long-term changes in cutaneous allergic and other inflammatory processes.

TL;DR: In this article, the authors investigated the role of CAMKK2 in melanoma cell death modality triggered by iron-dependent lipid peroxidation and showed that CAMKKII was prominently activated in ferroptosis.

TL;DR: In this article, the authors report the largest AK whole-exome sequencing study to date and perform a mutational signature and candidate driver gene analysis on these lesions, and demonstrate significant similarities between AKs and cSCC in terms of mutational burden, copy number alterations, mutational signatures, and patterns of gene mutations.

TL;DR: Progress to date including dissection of heritability, discovery of vitiligo susceptibility loci through candidate gene, genomewide linkage, andgenomewide association studies, relationships to other autoimmune diseases, polygenic architecture of vitILigo risk, vitiliga triggering, and disease onset are summarized and suggestions for future directions are provided.

TL;DR: It is demonstrated that the autocrine circuit of IL-33 in keratinocytes promotes the progression of psoriatic skin inflammation and IL- 33 is a potential therapeutic target of psoriasis.