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Granuloma annulare exhibits mixed immune and macrophage polarization profiles with spatial transcriptomics

ABSTRACT: Granuloma annulare exhibits mixed immune and macrophage polarization profiles with spatial transcriptomics

PROVIDER: PRJNA1098078 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28602500_1.fastq.gz	Fastqsanger.gz
	SRR28602500_2.fastq.gz	Fastqsanger.gz
	SRR28602501_1.fastq.gz	Fastqsanger.gz
	SRR28602501_2.fastq.gz	Fastqsanger.gz
	SRR28602502_1.fastq.gz	Fastqsanger.gz

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Granuloma annulare exhibits mixed immune and macrophage polarization profiles with spatial transcriptomics

Project description:Granuloma annulare (GA) is an idiopathic condition characterized by granulomatous inflammation in the skin. Prior studies have suggested that GA develops from various triggers, leading to a complex interplay involving innate and adaptive immunity, tissue remodeling, and fibrosis. Macrophages are the major immune cells comprising GA granulomas, however, the molecular drivers and inflammatory signaling cascade behind macrophage activation is poorly understood. Histologically, GA exhibits both palisaded and interstitial patterns on histology, however the molecular composition of GA at the spatial level remains unexplored. GA is a condition without FDA-approved therapies despite the significant impact of GA on quality of life. Spatial transcriptomics is a valuable tool for profiling localized, genome-wide gene expression changes across tissue with emerging applications in clinical medicine. To improve our understanding of the spatially localized gene expression patterns underlying GA, we profiled the spatial gene expression landscape from six patients with GA. Our findings revealed mixed Th1 and Th2 signals comprising the GA microenvironment and spatially distinct M1 and M2 macrophage polarization characteristics. IFN- and TNF signals emerged as important regulators of GA granulomatous inflammation and interleukin-32 emerged as a key driver of granulomatous inflammation. Overall, our spatial transcriptomics data indicate that GA exhibits mixed immune and macrophage polarization.

2024-05-12 | GSE263571 | GEO

Genome-wide expression profiling of leprosy and granuloma annulare skin lesions

Project description:Here we report the data generated by short-read sequencing of mRNA (polyA) isolated from granuloma annulare and leprosy skin lesions. Our main aim was to identify putative mRNA biomarkers for distinguishing leprosy from other differential diagnoses. Additionally, we also explored the distinction between MB and PB by using differential expression analysis as well as training a penalized logistic regression to select important features. Our results showed that few genes are enough to differentiate leprosy lesions, including paucibacillary cases, from other morphological and histopathological similar skin diseases. Some of these genes have been replicated in a larger and more heterogeneous sample with RT-qPCR, validating their classification potential. We also suggest important novel gene candidates to improve our understanding of molecular differences between MB and PB lesions, which could either pinpoint new pathways and targets for host-based specialized adjuvant treatment for leprosy. Finally, this dataset has been used to explore the relationship between cornification and keratinocyte-related genes and TGFB-mediated epithelial-mesenchymal transition (EMT), which could indicate that in skin, M. leprae could be de-differentiating, directly or indirectly, other cell types into a progenitor/stem-like phenotype, facilitating mycobacterial survival and migration within the host. Alternatively, this could highlight which pathways are activated during granuloma formation and/or skin barrier assembly/disassembly.

2021-10-01 | E-MTAB-10318 | biostudies-arrayexpress

Treatment of granuloma annulare and suppression of pro-inflammatory cytokine activity with tofacitinib [scRNA-Seq]

Project description:Granuloma annulare (GA) is a common inflammatory cutaneous disorder characterized by macrophage accumulation and activation in the skin. Its pathogenesis is poorly understood and there are no reliably effective treatments. Its potential health implications, if any, are unknown. Using single cell RNA sequencing (scRNAseq) we show that in GA, CD4+ T cells over-produce interferon (IFN)-g resulting in inflammatory polarization of macrophages and in altered extracellular matrix (ECM) production induced by the activity of oncostatin M, an interleukin (IL)-6 family cytokine, on fibroblasts. This mechanism identifies Janus kinase (JAK) inhibition as a potential therapeutic strategy, as both IFN-g and OSM signal via the JAK-STAT pathway. Indeed, treatment of five patients with severe, longstanding GA with tofacitinib (a JAK1/3 inhibitor) resulted in clinical and histologic disease remission in three patients and marked improvement in the other two. Treatment was associated with suppression of pathogenic cytokine activity in the skin and dissolution of macrophages. We also found that severe GA was associated with hypercytokinemia in plasma of patients, and JAK inhibition normalized this hypercytokiemia. Together, our results highlight the constitutive activity of the JAK-STAT pathway in GA as a result of IFN-g and OSM and identify JAK inhibitors as a potential molecularly targeted treatment for this disorder.

2020-12-22 | GSE158924 | GEO

Treatment of granuloma annulare and suppression of pro-inflammatory cytokine activity with tofacitinib [RNA-Seq]

2020-12-22 | GSE158923 | GEO

Genome-wide expression profiling of leprosy and granuloma annulare skin lesions

Project description:Genome-wide expression profiling of leprosy and granuloma annulare skin lesions

| PRJEB44217 | ENA

Treatment of granuloma annulare and suppression of pro-inflammatory cytokine activity with tofacitinib

Project description:Treatment of granuloma annulare and suppression of pro-inflammatory cytokine activity with tofacitinib

| PRJNA667031 | ENA

Treatment of granuloma annulare and suppression of pro-inflammatory cytokine activity with tofacitinib [scRNA-Seq]

Project description:Treatment of granuloma annulare and suppression of pro-inflammatory cytokine activity with tofacitinib [scRNA-Seq]

| PRJNA667044 | ENA

Treatment of granuloma annulare and suppression of pro-inflammatory cytokine activity with tofacitinib [RNA-Seq]

Project description:Treatment of granuloma annulare and suppression of pro-inflammatory cytokine activity with tofacitinib [RNA-Seq]

| PRJNA667045 | ENA

Treatment of granuloma annulare with tofacitinib 2% ointment.

Project description: Not available

| S-EPMC6940619 | biostudies-literature

An unusual orbital tumor in an adult: Granuloma annulare.

Project description:PurposeGranuloma annulare (GA) is a rare clinical entity that does not classically arise from the peri-orbital area in adults. The purpose of this case report is to present a 69-year-old female with GA of the orbit. As well, the pathological and immunohistochemical features of these tumors will be discussed.ObservationsOne case of GA of the orbit was identified from a tertiary ophthalmology referral centre. Clinical and histopathological features of the case were reviewed. Other cases of GA were also retrieved from the literature and addressed in this report.Conclusion and importanceGranuloma annulare is a rare orbital lesion in adults. It is known to typically arise on the hands and feet of children. This lesion must be distinguished from necrobiotic xanthogranuloma (NXG), which is a progressive peri-orbital dermatosis seen in middle age men and women. GA is thought to be a benign, often self-resolving condition, whereas NXG tends to be linked to other systemic conditions and may have a poorer prognosis.Differentiating this rare orbital tumor from necrobitotic xanthogranuloma (NXG) is essential, as both a systemic work-up and follow-up must be appropriately arranged. A comprehensive description of pathognomonic microscopic features of GA and NXG is reviewed to achieve the correct diagnosis.

| S-EPMC6247445 | biostudies-literature

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