Journal Of Investigative Dermatology

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Updated: 16 min 55 sec ago

Research Techniques Made Simple: CAR T Cell Therapy

Wed, 2018-09-19 00:00
Chimeric antigen receptor (CAR) and chimeric autoantibody receptor T cell therapy hold great promise in the treatment of cancer and autoimmune disease, respectively. This powerful technique involves genetically engineering T lymphocytes to enable selective destruction of disease-causing cells. In the current approach, a patient’s T cells are genetically engineered to express an antigen-specific antibody fragment fused to activating cytoplasmic T cell signaling domains. Following ex vivo activation and genetic modification of a patient’s own T cells, the individually-tailored CAR T cells are then infused into the patient for the selective destruction of cells bearing the targeted antigen.

Marked Changes in Lamellar Granule and Trans-Golgi Network Structure Occur During Epidermal Keratinocyte Differentiation

Tue, 2018-09-18 00:00
Epidermal lamellar granules (LGs) transport various lipids, proteins and protein inhibitors from the trans-Golgi network (TGN) to the extracellular space, and play an important role in skin barrier formation. We elucidated the three-dimensional (3D) structure of LGs and the TGN in normal human skin by focused ion beam scanning electron microscopy (FIB-SEM). Reconstructed FIB-SEM 3D images revealed that the overall LG structure changed from vesicular to reticular within the second layer of the stratum granulosum.

Both sphingosine kinase 1 and 2 coordinately regulate cathelicidin antimicrobial peptide production during keratinocyte differentiation

Sat, 2018-09-15 00:00
The innate immune element, cathelicidin antimicrobial peptide (CAMP), is vital in the formation of the antimicrobial barrier in skin. CAMP production is increased during epidermal differentiation and enriched in the stratum corneum. We recently identified an endoplasmic reticulum (ER) stress-mediated sphingosine-1-phosphate (S1P)- dependent mechanism of CAMP synthesis. Interestingly, in this study, we found that S1P synthesized by an isoform of sphingosine kinase (SPHK), SPHK1, serves as a signal for CAMP synthesis; and conversely, another isoform SPHK2 likely has a suppressor role or no role in CAMP production.

Increased myeloid dendritic cells and TNF-α expression predicts poor response to hydroxychloroquine in cutaneous lupus erythematosus

Sat, 2018-09-15 00:00
Although antimalarials are the primary treatment for cutaneous lupus erythematosus (CLE), not all patients are equally responsive. We investigated whether different inflammatory cell population and cytokine profiles in lesional CLE skin could affect the antimalarial responsiveness, and if hydroxychloroquine (HCQ) and quinacrine (QC) differentially suppress inflammatory cytokines.CLE patients were grouped according to their response to antimalarials (HCQ vs HCQ+QC). On immunohistochemistry, only the myeloid dendritic cell population was significantly increased in the HCQ+QC group compared to HCQ group.

Th1 and Th17 immune responses act complementarily to optimally control superficial dermatophytosis

Sat, 2018-09-15 00:00
Dermatophytoses are among the most common fungal infections worldwide but little is known about the immune response in them. By comparing Trichophyton benhamiae acute superficial dermatophytosis in WT and Rag2−/− mice, we showed that TCR-mediated immunity is critical for fungal clearance and clinical recovery. In WT mice, CD4+ T-cells isolated from the skin-draining lymph nodes exhibit both Th1 and Th17 differentiation during infection, with regard to produced cytokines or mRNA levels of transcription factors.

Spironolactone depletes the XPB protein and inhibits DNA damage responses in UVB-irradiated human skin

Sat, 2018-09-15 00:00
UVB wavelengths of light induce the formation of photoproducts in genomic DNA that are potentially mutagenic and detrimental to epidermal cell function. Interestingly, the mineralocorticoid and androgen receptor antagonist spironolactone (SP) was recently identified as an inhibitor of UV photoproduct removal in human cancer cells in vitro via its ability to promote the rapid proteolytic degradation of the DNA repair protein XPB (xeroderma pigmentosum group B). Using normal human keratinocytes in vitro and skin explants ex vivo, we find that SP rapidly depleted XPB protein in both systems and abrogated two major responses to UVB-induced DNA damage, including the removal of UV photoproducts from genomic DNA and the activation of the ATR/ATM DNA damage kinase signaling.

Insights into ZIKV-Mediated Innate Immune Responses in Human Dermal Fibroblasts and Epidermal Keratinocytes

Wed, 2018-09-12 00:00
Zika virus (ZIKV) has emerged as a global pathogen causing significant public health concern. ZIKV infections in humans principally occur via mosquito bites. Thus, host skin cells are permissive to ZIKV infection and are the first line of defense against the virus. Here, we examined the role and mechanisms of antiviral skin immunity against ZIKV infection. ZIKV infection (African lineage MR766) in human dermal fibroblasts (HDFs), human epidermal keratinocytes (HEKn), and HaCaT keratinocytes resulted in distinct expression changes in retinoic acid-inducible gene (RIG-I)-like receptors (RLR), such as RIG-I and melanoma differentiation-associated gene 5 (MDA5).

Hydrogel from acellular porcine adipose tissue accelerates wound healing by inducing intradermal adipocyte regeneration

Thu, 2018-09-06 00:00
As an important component of the skin, intradermal adipocytes are closely associated with skin homeostasis and wound healing. Although studies have focused on the role of fibroblasts, keratinocytes, and inflammatory cells in wound healing, the role of adipocytes has not been fully investigated. Here, we verified whether the induction of adipocyte regeneration in a wound bed can effectively promote wound healing, finding that the hydrogel from acellular porcine adipose tissue (HAPA) in combination with adipose-derived stem cells (ADSCs)can induce in situ adipogenesis in the wound microenvironment.

Lineage identity and location within the dermis determine the function of papillary and reticular fibroblasts in human skin

Sat, 2018-09-01 00:00
Human skin dermis is comprised of the superficial papillary dermis and the reticular dermis in the lower layers, which can easily be distinguished histologically. In vitro analyses of fibroblasts from explant cultures from superficial and lower dermal layers suggest that human skin comprises at least two fibroblast lineages with distinct morphology, expression profiles and functions. However, while for mouse skin cell surface markers have been identified allowing the isolation of pure populations of one lineage or the other via fluorescence-activated cell sorting (FACS), this has not been achieved for human skin fibroblasts.

BJD Editor's Choice

Sat, 2018-09-01 00:00
Despite rosacea being a common facial skin disorder affecting middle-aged adults, its aetiology is unknown and pathogenesis uncertain. Activation of the host innate immune response has been identified as important. The Demodex mite population in the skin of these patients is significantly higher than in patients with healthy skin, suggesting that it may be of aetiological importance in this disorder. These authors from Ireland and Germany set out to determine the role of these mites in human skin and their potential to interact with the host immune system.

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