Host-environment interfaces such as the dermis comprise tissue macrophages as the most abundant resident immune cell type. Diverse tasks, i.e. to resist against invading pathogens, to attract bypassing immune cells from penetrating vessels and to aid tissue development and repair require a dynamic postnatal coordination of tissue macrophages specification. Here, we delineated the postnatal development of dermal macrophages and their differentiation into distinct subsets by adapting single cell transcriptomics, fate-mapping and tissue imaging. We thereby identified a small phenotypically and transcriptionally distinct subset of embryo-derived skin macrophages that was maintained and largely excluded from the overall postnatal exchange by monocytes. These macrophages specifically interacted with dermal sensory nerves, surveilled and trimmed the myelin sheets and regulated axon sprouting after mechanical injury. In summary, our data show long-lasting functional specification of macrophages in the dermis that is driven by step-wise adaptation to guiding structures and ensures codevelopment of ontogenetically distinct cells within the same compartment. Overall design: Single Cell Sequencing was performed on CD45+CD11b+CD64+Lin-(lineage B220, CD3, NK1.1, Siglec-F, Ly6G) CX3CR1 (low, mid, high) macrophage subsets from mouse dermis after enzymatic digestion
A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves.
Age, Specimen part, Cell line, Subject
View SamplesWe used microarrays to investigate differential gene expression in HEK293T cells after transfection of the transgene of Iroquois 1 (IRX1). Microarray analysis revealed differential gene expression patterns of HEK293T cells after transient expression of IRX1. In total 8400 genes were deregulated by IRX1.
The IRX1/HOXA connection: insights into a novel t(4;11)- specific cancer mechanism.
Cell line
View SamplesThe transcription factor SRF (serum response factor) mediates epilepsy mediated gene expression
SRF modulates seizure occurrence, activity induced gene transcription and hippocampal circuit reorganization in the mouse pilocarpine epilepsy model.
Specimen part, Treatment
View SamplesHereditary sensory and autonomic neuropathy type I (HSAN-I) is neurological disorder characterized by distal sensory neuron dysfunction, frequent infections, and ulcerative mutilations. It remains unknown if HSAN-I directly dampens protective immunity. Here we report that HSAN-I-causing mutations of serine palmitoyltransferase long chain base subunit 2 (SPTLC2) affect human T cell responses. T cell antigenic stimulation and inflammation induce SPTLC2 expression. Murine T cell-specific ablation of Sptlc2 fundamentally impairs antiviral T cell survival and effector function. Mechanistically, SPTLC2-deficiency reduces sphingolipid biosynthetic flux and causes a prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress and CD8+ T cell death. Antiviral CD8+ T cell responses are restored by supplementing sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Our study reveals that SPTLC2 underpins protective adaptive immunity by translating extracellular stimuli into intracellular anabolic signals and reducing cellular stress to maintain metabolic reprogramming sustainability Overall design: Triplicates of each group were used for RNA-seq. Four groups were studied: Wild-type and SPTLC2-deficient CD8+ T cells, harvested from either naïve mice (D0) or mice infected with LCMV Armstrong 8 days earlier (D8).
Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8<sup>+</sup> T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness.
Treatment, Subject
View SamplesAutoimmune pancreatitis (AIP) is a recently identified disease of the pancreas with unknown etiology and antigens. The aim of this study was to determine new target antigens and differentially regulated genes and proteins by means of transcriptomics and proteomics and to validate them in patients with autoimmune pancreatitis. Here we report a distinct downregulation at the RNA and protein level of pancreatic proteases (anionic trypsinogen, cationic trypsinogen, mesotrypsinogen, elastase IIIB) and pancreatic stone protein in autoimmune pancreatitis in comparison to alcohol-induced chronic pancreatitis.
Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process.
Sex, Age, Specimen part, Disease
View Samples