Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease.

Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics.

Regulatory T Cells Require CCR6 for Skin Migration and Local Suppression of Vitiligo.

Vitiligo is an autoimmune skin disease caused by melanocyte-targeting autoreactive CD8+ T cells. Regulatory T cells (Tregs) have been implicated in restraining vitiligo severity in both mouse models and human patients; however, whether they must be present in the skin for their suppressive function is still unclear. We observed uneven distribution of Tregs within different anatomical locations of mouse skin, which correlated with reduced depigmentation after vitiligo induction.

Lithography-Free Technology for the Preparation of Digital Microfluidic (DMF) Lab-Chips with Droplet Actuation by Optoelectrowetting (OEW).

Electrically conducting liquid droplets can be activated and moved by electrowetting-on-dielectric (EWOD) and optoelectrowetting (OEW). An important application is droplet manipulation in digital microfluidics (DMF, lab-on-a-chip 2.0) as a chip-sized chemical laboratory.

Microdroplet Actuation via Light Line Optoelectrowetting (LL-OEW).

Meanwhile, electrowetting-on-dielectric (EWOD) is a well-known phenomenon, even often exploited in active micro-optics to change the curvature of microdroplet lenses or in analytical chemistry with digital microfluidics (DMF, lab on a chip 2.0) to move/actuate microdroplets. Optoelectrowetting (OEW) can bring more flexibility to DMF because in OEW, the operating point of the lab chip is locally controlled by a beam of light, usually impinging onto the chip perpendicularly.

scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in T function.

Vitiligo is an autoimmune skin disease characterized by the targeted destruction of melanocytes by T cells. Cytokine signaling between keratinocytes and T cells results in CD8 T cell infiltration of vitiligo lesions, but the full scope of signals required to coordinate autoimmune responses is not completely understood. We performed single-cell RNA sequencing on affected and unaffected skin from patients with vitiligo, as well as healthy controls, to define the role of each cell type in coordinating autoimmunity during disease progression.

Doped or Quantum-Dot Layers as In Situ Etch-Stop Indicators for III/V Semiconductor Reactive Ion Etching (RIE) Using Reflectance Anisotropy Spectroscopy (RAS).

Reflectance anisotropy spectroscopy (RAS), which was originally invented to monitor epitaxial growth, can-as we have previously shown-also be used to monitor the reactive ion etching of III/V semiconductor samples in situ and in real time, as long as the etching rate is not too high and the abrasion at the etch front is not totally chaotic. Moreover, we have proven that-using RAS equipment and optical Fabry‒Perot oscillations due to the ever-shrinking thickness of the uppermost etched layer-the in situ etch-depth resolution can be as good as ±0.8 nm, employing a Vernier-scale type measurement and evaluation procedure.

T-cell positioning by chemokines in autoimmune skin diseases.

Autoimmune skin diseases are complex processes in which autoreactive cells must navigate through the skin tissue to find their targets. Regulatory T cells in the skin help to mitigate autoimmune inflammation and may in fact be responsible for the patchy nature of these conditions. In this review, we will discuss chemokines that are important for global recruitment of T cell populations to the skin during disease, as well as signals that fine-tune their localization and function.

Resident Memory and Recirculating Memory T Cells Cooperate to Maintain Disease in a Mouse Model of Vitiligo.

Tissue resident memory T cells (Trm) form in the skin in vitiligo and persist to maintain disease, as white spots often recur rapidly after discontinuing therapy. We and others have recently described melanocyte-specific autoreactive Trm in vitiligo lesions. Here, we characterize the functional relationship between Trm and recirculating memory T cells (Tcm) in our vitiligo mouse model.

Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo.

Vitiligo is an autoimmune disease of the skin mediated by CD8 T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (T) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses.

Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure.

Background: Vitiligo is an autoimmune disease in which cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors.

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity.

Background: Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies.

Objective: To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects.

Methods: Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid.

Precise in situ etch depth control of multilayered III-V semiconductor samples with reflectance anisotropy spectroscopy (RAS) equipment.

Reflectance anisotropy spectroscopy (RAS) equipment is applied to monitor dry-etch processes (here specifically reactive ion etching (RIE)) of monocrystalline multilayered III-V semiconductors in situ. The related accuracy of etch depth control is better than 16 nm. Comparison with results of secondary ion mass spectrometry (SIMS) reveals a deviation of only about 4 nm in optimal cases.

Understanding mechanisms of autoimmunity through translational research in vitiligo.

Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells.

Lung dendritic cells imprint T cell lung homing and promote lung immunity through the chemokine receptor CCR4.

T cell trafficking into the lung is critical for lung immunity, but the mechanisms that mediate T cell lung homing are not well understood. Here, we show that lung dendritic cells (DCs) imprint T cell lung homing, as lung DC-activated T cells traffic more efficiently into the lung in response to inhaled antigen and at homeostasis compared with T cells activated by DCs from other tissues. Consequently, lung DC-imprinted T cells protect against influenza more effectively than do gut and skin DC-imprinted T cells.

Compartmentalized chemokine-dependent regulatory T-cell inhibition of allergic pulmonary inflammation.

Background: Induction of endogenous regulatory T (Treg) cells represents an exciting new potential modality for treating allergic diseases, such as asthma. Treg cells have been implicated in the regulation of asthma, but the anatomic location in which they exert their regulatory function and the mechanisms controlling the migration necessary for their suppressive function in asthma are not known. Understanding these aspects of Treg cell biology will be important for harnessing their power in the clinic.

Estrogen administration attenuates bladder outlet obstruction induced oxidative stress in the female rabbit.

Aims: Estrogen administration to female rabbits induces a functional hypertrophy of the bladder. The aim of this study was to investigate whether supplementation of estrogen in the female rabbit with partial bladder outlet obstruction (PBOO) would affect the severity of bladder dysfunction.

Methods: We surgically created PBOO in female New Zealand White rabbits.

Cloning, expression and characterization of insulin-degrading enzyme from tomato (Solanum lycopersicum).

A cDNA encoding insulin-degrading enzyme (IDE) was cloned from tomato (Solanum lycopersicum) and expressed in Escherichia coli in N-terminal fusion with glutathione S-transferase. GST-SlIDE was characterized as a neutral thiol-dependent metallopeptidase with insulinase activity: the recombinant enzyme cleaved the oxidized insulin B chain at eight peptide bonds, six of which are also targets of human IDE. Despite a certain preference for proline in the vicinity of the cleavage site, synthetic peptides were cleaved at apparently stochastic positions indicating that SlIDE, similar to IDEs from other organisms, does not recognize any particular amino acid motif in the primary structure of its substrates.

Crystal structure of 12-oxophytodienoate reductase 3 from tomato: self-inhibition by dimerization.

12-Oxophytodienoate reductase (OPR) 3, a homologue of old yellow enzyme (OYE), catalyzes the reduction of 9S,13S-12-oxophytodienoate to the corresponding cyclopentanone, which is subsequently converted to the plant hormone jasmonic acid (JA). JA and JA derivatives, as well as 12-oxophytodienoate and related cyclopentenones, are known to regulate gene expression in plant development and defense. Together with other oxygenated fatty acid derivatives, they form the oxylipin signature in plants, which resembles the pool of prostaglandins in animals.

Molecular analysis and organization of the sigmaB operon in Staphylococcus aureus.

The alternative sigma factor sigma(B) of Staphylococcus aureus controls the expression of a variety of genes, including virulence determinants and global regulators. Genetic manipulations and transcriptional start point (TSP) analyses showed that the sigB operon is transcribed from at least two differentially controlled promoters: a putative sigma(A)-dependent promoter, termed sigB(p1), giving rise to a 3.6-kb transcript covering sa2059-sa2058-rsbU-rsbV-rsbW-sigB, and a sigma(B)-dependent promoter, sigB(p3), initiating a 1.

The novel imidazopyridine 2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine (BYK191023) is a highly selective inhibitor of the inducible nitric-oxide synthase.

We have identified imidazopyridine derivatives as a novel class of NO synthase inhibitors with high selectivity for the inducible isoform. 2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine (BYK191023) showed half-maximal inhibition of crudely purified human inducible (iNOS), neuronal (nNOS), and endothelial (eNOS) NO synthases at 86 nM, 17 microM, and 162 microM, respectively. Inhibition of inducible NO synthase was competitive with l-arginine, pointing to an interaction of BYK191023 with the catalytic center of the enzyme.

Role of the degree of oligomerization in the structure and function of human surfactant protein A.

The role of the degree of oligomerization in the structure and function of human surfactant protein A (SP-A) was investigated using a human SP-A1 mutant (SP-A1(DeltaAVC,C6S)), expressed in mammalian cells, resulting from site-directed substitution of serine for Cys(6) and substitution of a functional signal peptide for the cysteine-containing SP-A signal sequence. This Cys(6) mutant lacked the NH(2)-terminal Ala(-3)-Val(-2)-Cys(-1) (DeltaAVC) extension present in some SP-A1 isoforms. SP-A1(DeltaAVC,C6S) was assembled exclusively as trimers as detected by electron microscopy and size exclusion chromatography.