Project description:Background: Scalp psoriasis presents distinct clinical features and treatment resistance compared to lesions on other body sites, yet its immune landscape remains poorly characterized. Methods: We performed single-cell RNA sequencing (scRNA-seq) on CD45⁺ immune cells from scalp and body plaque lesions of psoriasis patients and healthy controls. A total of 41,438 immune cells were analyzed. Downstream analyses included clustering, gene set enrichment, pseudotime trajectory inference, and cell–cell interaction modeling. Multiplex immunofluorescence was used to validate spatial co-localization. Results: Scalp psoriasis lesions exhibited a higher abundance of IL17⁺ CD8⁺ tissue-resident memory T (Tc17) cells, which co-expressed IFNG and lipid transporter FATP2 (SLC27A2). Pseudotime analysis revealed a trajectory from IL7R⁺ Trm cells toward Tc17 cells, especially enriched in the scalp. Trem2⁺ macrophages in scalp lesions showed increased expression of inflammatory mediators and MHC-I molecules. CellChat revealed enhanced MHC-I–mediated interactions between Trem2⁺ macrophages and Tc17 cells in the scalp. These interactions were confirmed by immunofluorescence, demonstrating co-localization of FATP2⁺ Tc17 and Trem2⁺ macrophages around sebaceous units. Conclusions: This study defines a scalp-specific pathogenic axis involving Trem2⁺ macrophages and FATP2⁺ Tc17 cells, potentially explaining the localization and persistence of inflammation in scalp psoriasis. Targeting lipid metabolism or specific cell–cell interactions may provide new therapeutic avenues for treatment-resistant scalp psoriasis.
2025-07-17 | GSE302456 | GEO
Project description:Study of microbial diversity on the scalp
Project description:Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis on other skin areas. We sought to determine the cellular and mollecular phenotype of scalp psoriasis by performing a comparative analysis of scalp vs skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement, and 10 control subjects without psoriasis. Our results suggest that even in the scalp psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprinting were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with skin psoriasis which was mainly associated with activation of TNFâµ/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes. To define the transcriptomic profile of scalp skin, punch biopsies (6 mm diameter) were obtained from 20 Caucasian patients with untreated moderate to severe psoriasis with significative scalp involvement and 10 control subjects without psoriasis (N). Lesional (LS) samples were isolated from the infiltrated border of a plaque of psoriasis. Non lesional (NL) samples were taken from scalp areas with no visible psoriasis between the infiltrated plaques.
Project description:Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate aging associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 old (age>18 years) and 4 young (age 3-6 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in PBMC by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the old animals exhibited higher inflammatory biomarkers in plasma and lower CD4 T cells with altered distribution of naïve and memory T cell maturation subsets. The gut microbiome in old animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of old animals compared to the young. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile.
Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.
Project description:Three individual patient-originated (Scalp trauma; ages 37, 46 and 57) DPCs were used for the studies. Dermal papilla cells, derived from the frontal scalp of 3 women, were treated with normal medium (Ctrl group) and medium containing 10-7 M corticotropin-releasing hormone (CRH group) for 72 h. Proteins were extracted and digested with trypsin for 4D label-free quantitative proteomics (Shanghai Applied Protein Technology Co., Ltd.).