Single-Cell Profiling Reveals Global Immune Responses during the Progression of Murine Epidermal Neoplasms.

Immune cells determine the role of the tumor microenvironment during tumor progression, either suppressing tumor formation or promoting tumorigenesis. We analyzed the profile of immune cells in the tumor microenvironment of control mouse skins and skin tumors at the single-cell level. We identified 15 CD45 immune cell clusters, which broadly represent the most functionally characterized immune cell types including macrophages, Langerhans cells (LC), conventional type 1 dendritic cells (cDC1), conventional type 2 dendritic cells (cDC2), migratory/mature dendritic cells (mDC), dendritic epidermal T cells (DETC), dermal γδ T cells (γδT), T cells, regulatory T cells (Tregs), natural killer cells (NK), type 2 innate lymphoid cells (ILC2), neutrophils (Neu), mast cells (Mast), and two proliferating populations (Prolif.

Deep mutationally scanned (DMS) CHIKV E3/E2 virus library maps viral amino acid preferences and predicts viral escape mutants of neutralizing CHIKV antibodies.

As outbreaks of chikungunya virus (CHIKV), a mosquito-borne alphavirus, continue to present public health challenges, additional research is needed to generate protective and safe vaccines and effective therapeutics. Prior research has established a role for antibodies in mediating protection against CHIKV infection, and the early appearance of CHIKV-specific IgG or IgG neutralizing antibodies protects against progression to chronic CHIKV disease in humans. However, the importance of epitope specificity for these protective antibodies and how skewed responses contribute to development of acute and chronic CHIKV-associated joint disease remains poorly understood.

Dupilumab and Alopecia Areata: A Possible Combined or Disturbance Therapy? A Review of The Literature.

Introduction: Dupilumab, a monoclonal antibody targeting IL-4 receptor subunit alpha, treats atopic dermatitis (AD) and may impact alopecia areata (AA). AA involves Th1-driven immune activity, and recent studies suggest a role for Th2 pathways. Dupilumab's effects on AA are mixed, with reports of both improvement and worsening.

Uncommon Presentation of Pityriasis Rubra Pilaris of the Scalp: Clinical, Trichoscopic, and Histopathologic Features and Review of the Literature.

Pityriasis rubra pilaris (PRP) presents a diagnostic challenge due to its varied clinical manifestations and the scarce literature on scalp involvement. This article presents a case report of a 59-year-old female with PRP solely affecting the scalp, detailing its clinical, trichoscopic, and histopathological features. Trichoscopy revealed a novel finding of white-silvery scales forming hair casts with a triangular shape, distinct from the existing literature.

Screening of Anal HPV Precancerous Lesions: A Review after Last Recommendations.

Over the last decades, the incidence of anal cancer has increased worldwide. The discovery of the HPV virus as its primary cause and the natural progression of the disease, involving precancerous lesions, have resulted in significant interest in screening for anal cancer. The use of cytology testing, high-risk HPV DNA research, high-resolution anoscopy, and their combination has been adopted with variable success in detecting anal HPV precancerous lesions.

Vimentin regulates mitochondrial ROS production and inflammatory responses of neutrophils.

The intermediate filament vimentin is present in immune cells and is implicated in proinflammatory immune responses. Whether and how it supports antimicrobial activities of neutrophils are not well established. Here, we developed an immortalized neutrophil model to examine the requirement of vimentin.

Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8 T cell adoptive therapies in pre-clinical studies.

Mitochondrial respiration is essential for the survival and function of T cells used in adoptive cellular therapies. However, strategies that specifically enhance mitochondrial respiration to promote T cell function remain limited. Here, we investigate methylation-controlled J protein (MCJ), an endogenous negative regulator of mitochondrial complex I expressed in CD8 cells, as a target for improving the efficacy of adoptive T cell therapies.

Vimentin regulates mitochondrial ROS production and inflammatory responses of neutrophils.

The intermediate filament vimentin is present in immune cells and is implicated in proinflammatory immune responses. Whether and how it supports antimicrobial activities of neutrophils is not well established. Here, we developed an immortalized neutrophil model to examine the requirement of vimentin.

MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade.

Immune checkpoint inhibitors (ICIs) are now the first-line treatment for patients with advanced melanoma. Despite promising clinical results, many patients fail to respond to these therapies. BH3 mimetics, a novel class of small molecule inhibitors that bind and inhibit anti-apoptotic members of the BCL2 family proteins such as BCL2 or MCL1, have been very successful in treating hematologic malignancies.

Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine.

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine.

Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models.

The "innate-like" T cell compartment, known as T, represents a diverse group of T cells that straddle the boundary between innate and adaptive immunity, having the ability to mount rapid responses following activation. In mice, this ability is acquired during thymic development. We explored the transcriptional landscape of T compared to conventional T cells (T) in the human thymus and blood using single cell RNA sequencing and flow cytometry.

Identification of a DNA-cytosine methyltransferase that impacts global transcription to promote group B streptococcal vaginal colonization.

Group B (GBS) colonizes the female reproductive tract (FRT) in one-third of women, and carriage leads to numerous adverse pregnancy outcomes including the preterm premature rupture of membranes, chorioamnionitis, and stillbirth. The presence of GBS in the FRT during pregnancy is also the largest predisposing factor for the transmission of GBS and invasive neonatal diseases, including pneumonia, sepsis, and meningitis. The factors contributing to GBS colonization are still being elucidated.

A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy.

Unlabelled: The BCL2 inhibitor venetoclax has recently emerged as an important component of acute myeloid leukemia (AML) therapy. Notably, use of this agent has revealed a previously unrecognized form of pathogenesis characterized by monocytic disease progression. We demonstrate that this form of disease arises from a fundamentally different type of leukemia stem cell (LSC), which we designate as monocytic LSC (m-LSC), that is developmentally and clinically distinct from the more well-described primitive LSC (p-LSC).

Diagnostic Accuracy of Line-Field Confocal Optical Coherence Tomography for the Diagnosis of Skin Carcinomas.

Line-field confocal optical coherence tomography (LC-OCT) is a new, noninvasive imaging technique for the diagnosis of skin cancers. A total of 243 benign (54%) and malignant (46%) skin lesions were consecutively enrolled from 27 August 2020, to 6 October 2021 at the Dermatology Department of the University Hospital of Siena, Italy. Dermoscopic- and LC-OCT-based diagnoses were given by an expert dermatologist and compared with the ground truth.

Current insights in mouse iNKT and MAIT cell development using single cell transcriptomics data.

Innate T (T) cells are a collection of T cells with important regulatory functions that have a crucial role in immunity towards tumors, bacteria, viruses, and in cell-mediated autoimmunity. In mice, the two main αβ T cell subsets include the invariant NKT (iNKT) cells that recognize glycolipid antigens presented by non-polymorphic CD1d molecules and the mucosal associated invariant T (MAIT) cells that recognize vitamin B metabolites presented by the non-polymorphic MR1 molecules. Due to their ability to promptly secrete large quantities of cytokines either after T cell antigen receptor (TCR) activation or upon exposure to tissue- and antigen-presenting cell-derived cytokines, T cells are thought to act as a bridge between the innate and adaptive immune systems and have the ability to shape the overall immune response.

Antigens Expressed by Breast Cancer Cells Undergoing EMT Stimulate Cytotoxic CD8 T Cell Immunity.

Antigenic differences formed by alterations in gene expression and alternative splicing are predicted in breast cancer cells undergoing epithelial to mesenchymal transition (EMT) and the reverse plasticity known as MET. How these antigenic differences impact immune interactions and the degree to which they can be exploited to enhance immune responses against mesenchymal cells is not fully understood. We utilized a master microRNA regulator of EMT to alter mesenchymal-like EO771 mammary carcinoma cells to a more epithelial phenotype.

Discovering metabolite quantitative trait loci in asthma using an isolated population.

Background: Integration of metabolomics with genetics may advance understanding of disease pathogenesis but has been underused in asthma genetic studies.

Objective: We sought to discover new genetic effects in asthma and to characterize the molecular consequences of asthma genetic risk through integration with the metabolome in a homogeneous population.

Methods: From fasting serum samples collected on 348 Tangier Island residents, we quantified 2612 compounds using untargeted metabolomics.

Zika Virus Congenital Syndrome and gene variants: insights from a family of dizygotic twins.

Congenital Zika virus syndrome (CZS) is associated with damage to neural progenitor cells by ZIKA virus infection. There are no accurate statistics on the percentage of pregnant mothers who have had babies affected by the syndrome. Few cases of discordant twins have been described in the literature and, therefore, we hypothesize that the genetic background of the progeny and/or mother may play a role in the fate of the syndrome.

Thymic iNKT single cell analyses unmask the common developmental program of mouse innate T cells.

Most T lymphocytes leave the thymus as naïve cells with limited functionality. However, unique populations of innate-like T cells differentiate into functionally distinct effector subsets during their development in the thymus. Here, we profiled >10,000 differentiating thymic invariant natural killer T (iNKT) cells using single-cell RNA sequencing to produce a comprehensive transcriptional landscape that highlights their maturation, function, and fate decisions at homeostasis.

Deletion of p53 and Hyper-Activation of PIK3CA in Keratin-15 Stem Cells Lead to the Development of Spontaneous Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) is the second commonest type of skin cancer, and SCCs make up about 90% of head and neck cancers (HNSCCs). HNSCCs harbor two frequent molecular alterations, namely, gain-of-function alterations of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( and loss-of-function mutations of tumor protein p53 (). However, it remains poorly understood whether HNSCCs harboring different genetic alterations exhibit differential immune tumor microenvironments (TME).