Star products made (somewhat) easier

We develop an approach to the deformation quantization on the real plane with an arbitrary Poisson structure which based on Weyl symmetrically ordered operator products. By using a polydifferential representation for deformed coordinates $\hat x^j$ we are able to formulate a simple and effective iterative procedure which allowed us to calculate the fourth order star product (and may be extended to the fifth order at the expense of tedious but otherwise straightforward calculations). Modulo some cohomology issues which we do not consider here, the method gives an explicit and physics-friendly description of the star products.Comment: 20 pages, v2, v3: comments and references adde

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis.

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis

The OSCAR-MP consensus criteria for quality assessment of retinal optical coherence tomography angiography

BACKGROUND AND OBJECTIVES: Optical coherence tomography angiography (OCTA) is a noninvasive high-resolution imaging technique for assessing the retinal vasculature and is increasingly used in various ophthalmologic, neuro-ophthalmologic, and neurologic diseases. To date, there are no validated consensus criteria for quality control (QC) of OCTA. Our study aimed to develop criteria for OCTA quality assessment. METHODS: To establish criteria through (1) extensive literature review on OCTA artifacts and image quality to generate standardized and easy-to-apply OCTA QC criteria, (2) application of OCTA QC criteria to evaluate interrater agreement, (3) identification of reasons for interrater disagreement, revision of OCTA QC criteria, development of OCTA QC scoring guide and training set, and (4) validation of QC criteria in an international, interdisciplinary multicenter study. RESULTS: We identified 7 major aspects that affect OCTA quality: (O) obvious problems, (S) signal strength, (C) centration, (A) algorithm failure, (R) retinal pathology, (M) motion artifacts, and (P) projection artifacts. Seven independent raters applied the OSCAR-MP criteria to a set of 40 OCTA scans from people with MS, Sjogren syndrome, and uveitis and healthy individuals. The interrater kappa was substantial (? 0.67). Projection artifacts were the main reason for interrater disagreement. Because artifacts can affect only parts of OCTA images, we agreed that prior definition of a specific region of interest (ROI) is crucial for subsequent OCTA quality assessment. To enhance artifact recognition and interrater agreement on reduced image quality, we designed a scoring guide and OCTA training set. Using these educational tools, 23 raters from 14 different centers reached an almost perfect agreement (? 0.92) for the rejection of poor-quality OCTA images using the OSCAR-MP criteria. DISCUSSION: We propose a 3-step approach for standardized quality control: (1) To define a specific ROI, (2) to assess the occurrence of OCTA artifacts according to the OSCAR-MP criteria, and (3) to evaluate OCTA quality based on the occurrence of different artifacts within the ROI. OSCAR-MP OCTA QC criteria achieved high interrater agreement in an international multicenter study and is a promising QC protocol for application in the context of future clinical trials and studies

Single-cell characterisation of T lymphocyte immune responses in spondyloarthropathy

The spondyloarthropathies (SpA) are a collection of inflammatory disorders of undetermined etiology affecting the joints and connective tissues, however existing evidence suggests a role for the microbiome, CD4 and CD8 T cells in disease pathogenesis. A CD154 activation based functional assay was first used to quantify and characterise CD4+ memory T cell populations reactive to a panel of 13 microbes found at mucosal barrier sites, predominantly gut bacteria. Peripheral blood mononuclear cells (PBMC) from 31 SpA, 17 rheumatoid arthritis (RA) and 14 healthy controls, as well as synovial fluid mononuclear cells (SFMC) from 9 SpA patients were separated and stimulated overnight with a panel of microbial lysates. Cells were then stained for CD154, TNFα, IFNγ, IL-17A, GM-CSF, IL-22 and IL-2 and analysed by flow cytometry. Single-cell RNA sequencing (scRNA-seq) was then used to characterise S. typhimurium-reactive synovial Th memory cells from a psoriatic arthritis (PsA) patient, in addition to ex vivo CD4 and CD8 memory T cells from the peripheral blood and synovial fluid of 6 PsA patients. The frequency of Th memory cells reactive to microbes capable of inducing a type 17/17.1 response were enriched in SpA synovial fluid relative to blood, and scRNA-seq analysis revealed a trajectory along which Th17.1 cells could differentiate into a "stem-like" memory pool capable of proliferation or into a Th17 regulatory phenotype. Pronounced clonal expansions of ex vivo CD8 memory T-cells within the joints of PsA patients were also identified by scRNA-seq. They exhibited distinct gene expression profiles including cycling, activation, tissue homing and tissue residency markers. Pseudotime analysis of these clonal CD8 populations identified trajectories in which tissue residency can represent an intermediate developmental state giving rise to activated, cycling and exhausted CD8 populations. Comparing T cell clonality across patients further revealed specificity convergence of clones against a putative common antigen. A role for gut microbes in SpA pathogenesis was supported by the higher frequency of Th17 cells reactive to Salmonella typhimurium found in SpA synovial fluid compared with SpA peripheral blood, and characterisation of these cells revealed trajectories of differentiation which could potentially be targeted to skew Th17.1 responses towards a regulatory phenotype. The identification of pro-inflammatory and clonally expanded CD8 T cells by scRNA-seq also suggests an antigen driven expansion of pathogenic CD8 T cells in PsA.</p

Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates

Regulatory T cells (Tregs) play an important role in controlling inflammation and limiting autoimmunity, but their phenotypes at inflammatory sites in human disease are poorly understood. We here analyze the single-cell transcriptome of >16,000 Tregs obtained from peripheral blood and synovial fluid of two patients with HLA-B27+ ankylosing spondylitis and three patients with psoriatic arthritis, closely related forms of inflammatory spondyloarthritis. We identify multiple Treg clusters with distinct transcriptomic profiles, including, among others, a regulatory CD8+ subset expressing cytotoxic markers/genes, and a Th17-like RORC+ Treg subset characterized by IL-10 and LAG-3 expression. Synovial Tregs show upregulation of interferon signature and TNF receptor superfamily genes, and marked clonal expansion, consistent with tissue adaptation and antigen contact respectively. Individual synovial Treg clones map to different clusters indicating cell fate divergence. Finally, we demonstrate that LAG-3 directly inhibits IL-12/23 and TNF secretion by patient-derived monocytes, a mechanism with translational potential in SpA. Our detailed characterization of Tregs at an important inflammatory site illustrates the marked specialization of Treg subpopulations

miR-10b-5p is a novel Th17 regulator present in Th17 cells from Ankylosing Spondylitis

Objective: to determine the microRNA (miR) signature in ankylosing spondylitis (AS) Th17 cells.Methods: IL-17A-producing CD4+ T cells from AS patients and healthy controls were FACS-sorted for miR RNA sequencing and qPCR validation. miR-10b function was determined by miR mimic expression followed by cytokine measurement, transcriptome analysis, qPCR and luciferase assays. Results: AS Th17 cells exhibited a miR signature characterized by upregulation of miR-155-5p, miR- 210-3p and miR-10b. miR-10b has not been described previously in Th17 cells and was selected for further characterization. miR-10b is transiently induced in in-vitro differentiated Th17 cells. Transcriptome, qPCR and luciferase assays suggest that MAP3K7 is targeted by miR-10b. Both miR-10b over-expression and MAP3K7 silencing inhibited production of IL-17A by both total CD4 and differentiating Th17 cells. Conclusions: AS Th17 cells have a specific miR signature and upregulate miR-10b in vitro. Our data suggest that miR-10b is upregulated by pro-inflammatory cytokines and may act as a feedback loop to suppress IL-17A by targeting MAP3K7. miR-10b is a potential therapeutic candidate to suppress pathogenic Th17 cell function in AS patients.</p

miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis

Objective: To determine the microRNA (miR) signature in ankylosing spondylitis (AS) T helper (Th)17 cells. Methods: Interleukin (IL)-17A-producing CD4+ T cells from patients with AS and healthy controls were FACS-sorted for miR sequencing and qPCR validation. miR-10b function was determined by miR mimic expression followed by cytokine measurement, transcriptome analysis, qPCR and luciferase assays. Results: AS Th17 cells exhibited a miR signature characterised by upregulation of miR-155-5p, miR-210-3p and miR-10b. miR-10b has not been described previously in Th17 cells and was selected for further characterisation. miR-10b is transiently induced in in vitro differentiated Th17 cells. Transcriptome, qPCR and luciferase assays suggest that MAP3K7 is targeted by miR-10b. Both miR-10b overexpression and MAP3K7 silencing inhibited production of IL-17A by both total CD4 and differentiating Th17 cells. Conclusions: AS Th17 cells have a specific miR signature and upregulate miR-10b in vitro. Our data suggest that miR-10b is upregulated by proinflammatory cytokines and may act as a feedback loop to suppress IL-17A by targeting MAP3K7. miR-10b is a potential therapeutic candidate to suppress pathogenic Th17 cell function in patients with AS

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis