scholarly journals Elucidating the immune infiltration in acne and its comparison with rosacea by integrated bioinformatics analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248650
Author(s):  
Lu Yang ◽  
Yan-Hong Shou ◽  
Yong-Sheng Yang ◽  
Jin-Hua Xu

Background Acne vulgaris and rosacea are common inflammatory complications of the skin, both characterized by abnormal infiltration of immune cells. The two diseases can be differentiated based on characteristic profile of the immune cell infiltrates at the periphery of disease lesions. In addition, dysregulated infiltration of immune cells not only occur in the acne lesions but also in non-lesional areas of patients with the disease, thus characterizing the immune infiltration in these sites can further enhance our understanding on the pathogenesis of acne. Methods Five microarray data-sets (GSE108110, GSE53795, GSE65914, GSE14905 and GSE78097) were downloaded from Gene Expression Omnibus. After removing the batch effects and normalizing the data, we applied the CIBERSORT algorithm combined with signature matrix LM22, to describe 22 types of immune cells’ infiltration in acne less than 48 hour (H) old, in comparation with non-lesional skin of acne patients, healthy skin and rosacea (including erythematotelangiectatic rosacea, papulopustular rosacea and phymatous rosacea) and we compared gene expression of Th1 and Th17-related molecules in acne, rosacea and healthy control. Results Compared with the non-lesional skin of acne patients, healthy individuals and rosacea patients, there is a significant increase in infiltration of neutrophils, monocytes and activated mast cells around the acne lesions, less than 48 H after their development. Contrarily, few naive CD4+ T cells, plasma cells, memory B cells and resting mast cells infiltrate acne sites compared to the aforementioned groups of individuals. Moreover, the infiltration of Regulatory T cells (Tregs) in acne lesions is substantially lower, relative to non-lesional sites of acne patients and skin of healthy individuals. In addition, non-lesional sites of acne patients exhibit lower infiltration of activated memory CD4+ T cells, plasma cells, memory B cells, M0 macrophages, neutrophils, resting mast cells but higher infiltration of Tregs and resting dendritic cells relative to skin of healthy individuals. Intriguingly, we found that among the 3 rosacea subtypes, the immune infiltration profile of papulopustular rosacea is the closest to that of acne lesions. In addition, through gene expression analysis of acne, rosacea and skin tissues of healthy individuals, we found a higher infiltration of Th1 and Th17 cells in acne lesions, relative to non-lesional skin areas of acne patients. Conclusions Our study provides new insights into the inflammatory pathogenesis of acne, and the difference between acne and rosacea, which helps in differentiating the two diseases. Our findings also guide on appropriate target therapy of the immune cell infiltrates in the two disease conditions.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei Li ◽  
Zheng Zhang ◽  
Zuo-min Wang

Abstract Background Host immunity plays an important role against oral microorganisms in periodontitis. Methods This study assessed the infiltrating immune cell subtypes in 133 healthy periodontal and 210 chronic periodontitis tissues from Gene Expression Omnibus (GEO) datasets using the CIBERSORT gene signature files. Results Plasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues, when compared to those in healthy controls. In contrast, memory B cells, resting dendritic, mast cells and CD4 memory cells, as well as activated mast cells, M1 and M2 macrophages, and follicular helper T cells, were mainly present in healthy periodontal tissues. Furthermore, these periodontitis tissues generally contained a higher proportion of activated CD4 memory T cells, while the other subtypes of T cells, including resting CD4 memory T cells, CD8 T cells, follicular helper T cells (TFH) and regulatory T cells (Tregs), were relatively lower in periodontitis tissues, when compared to healthy tissues. The ratio of dendritic and mast cells and macrophages was lower in periodontitis tissues, when compared to healthy tissues. In addition, there was a significant negative association of plasma cells with most of the other immune cells, such as plasma cells vs. memory B cells (γ = − 0.84), plasma cells vs. resting dendritic cells (γ = − 0.64), plasma cells vs. resting CD4 memory T cells (γ = 0.50), plasma cells versus activated dendritic cells (γ = − 0.46), plasma cells versus TFH (γ = − 0.46), plasma cells versus macrophage M2 cells (γ = − 0.43), or plasma cells versus macrophage M1 cells (γ = − 0.40), between healthy control and periodontitis tissues. Conclusion Plasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues. The infiltration of different immune cell subtypes in the periodontitis site could lead the host immunity against periodontitis.


2021 ◽  
Author(s):  
Sheng Fang ◽  
Xiao Fang ◽  
Xin Xu ◽  
Lin Zhong ◽  
An-quan Wang ◽  
...  

Abstract Relevance Rheumatoid arthritis (RA) is a systemic autoimmune disease with an aggressive, chronic synovial inflammation as the main pathological change. However, the specific etiology, pathogenesis, and related biomarkers in diagnosis and treatment are still not fully elucidated. This study attempts to provide new perspectives and insights into RA at the genetic, molecular, and cellular levels through the tenet of personalized medicine. Methods Gene expression profiles of four individual knee synovial tissues were downloaded from a comprehensive gene expression database, R language was used to screen for significantly differentially expressed genes (DEGs), Gene Ontology Enrichment Analysis, Kyoto Gene Encyclopedia, and Gene Set Enrichment Analysis were performed to analyze the biological functions and signaling pathways of these DEGs, STRING online database was used to establish protein-protein interaction networks, Cytoscape software to obtain ten hub genes, Goplot to get six inflammatory immune-related hub genes, and CIBERSORT algorithm to impute immune infiltration. Results Molecular pathways that play important roles in RA were obtained: Toll-like receptors, AMPK, MAPK, TNF, FoxO, TGF-beta, PI3K and NF-κB pathways, Ten hub genes: Ccr1, Ccr2, Ccr5, Ccr7, Cxcl5, Cxcl6, Cxcl13, Ccl13, Adcy2, and Pnoc. among which Adcy2 and Pnoc have not been reported in RA studies, suggesting that they may be worthy targets for further study. It was also found that among the synoviocytes in RA, the proportions of plasma cells, CD8 T cells, follicular helper T cells, monocytes, γ delta T cells, and M0 macrophages were higher, while the proportions of CD4 memory resting T cells, regulatory T cells (Tregs), activated NK cells, resting dendritic cells, M1 macrophages, eosinophils, activated mast cells, resting mast cells were lower in proportion, and each cell played an important role in RA. Conclusions This study may help understand the key genes, molecular pathways, the role of inflammatory immune infiltrating cells in RA’s pathogenesis and provide new targets and ideas for the diagnosis and personalized treatment of RA.


2020 ◽  
Vol 2020 ◽  
pp. 1-21 ◽  
Author(s):  
Ziming Chen ◽  
Yuanchen Ma ◽  
Xuerui Li ◽  
Zhantao Deng ◽  
Minghao Zheng ◽  
...  

Background. Immunological mechanisms play a vital role in the pathogenesis of knee osteoarthritis (KOA). Moreover, the immune phenotype is a relevant prognostic factor in various immune-related diseases. In this study, we used CIBERSORT for deconvolution of global gene expression data to define the immune cell landscape of different structures of knee in osteoarthritis. Methods and Findings. By applying CIBERSORT, we assessed the relative proportions of immune cells in 76 samples of knee cartilage, 146 samples of knee synovial tissue, 40 samples of meniscus, and 50 samples of knee subchondral bone. Enumeration and activation status of 22 immune cell subtypes were provided by the obtained immune cell profiles. In synovial tissues, the differences in proportions of plasma cells, M1 macrophages, M2 macrophages, activated dendritic cells, resting mast cells, and eosinophils between normal tissues and osteoarthritic tissues were statistically significant (P<0.05). The area under the curve was relatively large in resting mast cells, dendritic cells, and M2 macrophages in receiver operating characteristic analyses. In subchondral bones, the differences in proportions of resting master cells and neutrophils between normal tissues and osteoarthritic tissues were statistically significant (P<0.05). In subchondral bones, the proportions of immune cells, from the principle component analyses, displayed distinct group-bias clustering. Resting mast cells and T cell CD8 were the major component of first component. Moreover, we revealed the potential interaction between immune cells. There was almost no infiltration of immune cells in the meniscus and cartilage of the knee joint. Conclusions. The immune cell composition in KOA differed substantially from that of healthy joint tissue, while it also differed in different anatomical structures of the knee. Meanwhile, activated mast cells were mainly associated with high immune cell infiltration in OA. Furthermore, we speculate M2 macrophages in synovium and mast cells in subchondral bone may play an important role in the pathogenesis of OA.


2017 ◽  
Vol 313 (5) ◽  
pp. E528-E539 ◽  
Author(s):  
Katya B. Rubinow ◽  
Jing H. Chao ◽  
Derek Hagman ◽  
Mario Kratz ◽  
Brian Van Yserloo ◽  
...  

Male hypogonadism results in changes in body composition characterized by increases in fat mass. Resident immune cells influence energy metabolism in adipose tissue and could promote increased adiposity through paracrine effects. We hypothesized that manipulation of circulating sex steroid levels in healthy men would alter adipose tissue immune cell populations. Subjects ( n = 44 men, 19–55 yr of age) received 4 wk of treatment with the gonadotropin-releasing hormone receptor antagonist acyline with daily administration of 1) placebo gel, 2) 1.25 g testosterone gel (1.62%), 3) 5 g testosterone gel, or 4) 5 g testosterone gel with an aromatase inhibitor. Subcutaneous adipose tissue biopsies were performed at baseline and end-of-treatment, and adipose tissue immune cells, gene expression, and intra-adipose estrogen levels were quantified. Change in serum total testosterone level correlated inversely with change in the number of CD3+ (β = −0.36, P = 0.04), CD4+ (β = −0.34, P = 0.04), and CD8+ (β = −0.33, P = 0.05) T cells within adipose tissue. Change in serum 17β-estradiol level correlated inversely with change in the number of adipose tissue macrophages (ATMs) (β = −0.34, P = 0.05). A negative association also was found between change in serum testosterone and change in CD11c+ ATMs (β = −0.41, P = 0.01). Overall, sex steroid deprivation was associated with increases in adipose tissue T cells and ATMs. No associations were found between changes in serum sex steroid levels and changes in adipose tissue gene expression. Circulating sex steroid levels may regulate adipose tissue immune cell populations. These exploratory findings highlight a possible novel mechanism that could contribute to increased metabolic risk in hypogonadal men.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiu-Yue Zhong ◽  
Er-Xi Fan ◽  
Guang-Yong Feng ◽  
Qi-Ying Chen ◽  
Xiao-Xia Gou ◽  
...  

Abstract Object Glioma is a common malignant tumours in the central nervous system (CNS), that exhibits high morbidity, a low cure rate, and a high recurrence rate. Currently, immune cells are increasingly known to play roles in the suppression of tumourigenesis, progression and tumour growth in many tumours. Therefore, given this increasing evidence, we explored the levels of some immune cell genes for predicting the prognosis of patients with glioma. Methods We extracted glioma data from The Cancer Genome Atlas (TCGA). Using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, the relative proportions of 22 types of infiltrating immune cells were determined. In addition, the relationships between the scales of some immune cells and sex/age were also calculated by a series of analyses. A P-value was derived for the deconvolution of each sample, providing credibility for the data analysis (P < 0.05). All analyses were conducted using R version 3.5.2. Five-year overall survival (OS) also showed the effectiveness and prognostic value of each proportion of immune cells in glioma; a bar plot, correlation-based heatmap (corheatmap), and heatmap were used to represent the proportions of immune cells in each glioma sample. Results In total, 703 transcriptomes from a clinical dataset of glioma patients were drawn from the TCGA database. The relative proportions of 22 types of infiltrating immune cells are presented in a bar plot and heatmap. In addition, we identified the levels of immune cells related to prognosis in patients with glioma. Activated dendritic cells (DCs), eosinophils, activated mast cells, monocytes and activated natural killer (NK) cells were positively related to prognosis in the patients with glioma; however, resting NK cells, CD8+ T cells, T follicular helper cells, gamma delta T cells and M0 macrophages were negatively related to prognosis in the patients with glioma. Specifically, the proportions of several immune cells were significantly related to patient age and sex. Furthermore, the level of M0 macrophages was significant in regard to interactions with other immune cells, including monocytes and gamma delta T cells, in glioma tissues through sample data analysis. Conclusion We performed a novel gene expression-based study of the levels of immune cell subtypes and prognosis in glioma, which has potential clinical prognostic value for patients with glioma.


Author(s):  
Xin Liu ◽  
Guo-Ping Shi ◽  
Junli Guo

Pressure overload and heart failure are among the leading causes of cardiovascular morbidity and mortality. Accumulating evidence suggests that inflammatory cell activation and release of inflammatory mediators are of vital importance during the pathogenesis of these cardiac diseases. Yet, the roles of innate immune cells and subsequent inflammatory events in these processes remain poorly understood. Here, we outline the possible underlying mechanisms of innate immune cell participation, including mast cells, macrophages, monocytes, neutrophils, dendritic cells, eosinophils, and natural killer T cells in these pathological processes. Although these cells accumulate in the atrium or ventricles at different time points after pressure overload, their cardioprotective or cardiodestructive activities differ from each other. Among them, mast cells, neutrophils, and dendritic cells exert detrimental function in experimental models, whereas eosinophils and natural killer T cells display cardioprotective activities. Depending on their subsets, macrophages and monocytes may exacerbate cardiodysfunction or negatively regulate cardiac hypertrophy and remodeling. Pressure overload stimulates the secretion of cytokines, chemokines, and growth factors from innate immune cells and even resident cardiomyocytes that together assist innate immune cell infiltration into injured heart. These infiltrates are involved in pro-hypertrophic events and cardiac fibroblast activation. Immune regulation of cardiac innate immune cells becomes a promising therapeutic approach in experimental cardiac disease treatment, highlighting the significance of their clinical evaluation in humans.


2021 ◽  
Vol 12 ◽  
Author(s):  
Miranda Houtman ◽  
Espen Hesselberg ◽  
Lars Rönnblom ◽  
Lars Klareskog ◽  
Vivianne Malmström ◽  
...  

HLA-DRB1 alleles have been associated with several autoimmune diseases. For anti-citrullinated protein antibody positive rheumatoid arthritis (RA), HLA-DRB1 shared epitope (SE) alleles are the major genetic risk factors. In order to study the genetic regulation of major histocompatibility complex (MHC) Class II gene expression in immune cells, we investigated transcriptomic profiles of a variety of immune cells from healthy individuals carrying different HLA-DRB1 alleles. Sequencing libraries from peripheral blood mononuclear cells, CD4+ T cells, CD8+ T cells, and CD14+ monocytes of 32 genetically pre-selected healthy female individuals were generated, sequenced and reads were aligned to the standard reference. For the MHC region, reads were mapped to available MHC reference haplotypes and AltHapAlignR was used to estimate gene expression. Using this method, HLA-DRB and HLA-DQ were found to be differentially expressed in different immune cells of healthy individuals as well as in whole blood samples of RA patients carrying HLA-DRB1 SE-positive versus SE-negative alleles. In contrast, no genes outside the MHC region were differentially expressed between individuals carrying HLA-DRB1 SE-positive and SE-negative alleles, thus HLA-DRB1 SE alleles have a strong cis effect on gene expression. Altogether, our findings suggest that immune effects associated with different allelic forms of HLA-DR and HLA-DQ may be associated not only with differences in the structure of these proteins, but also with differences in their expression levels.


2021 ◽  
Vol 30 ◽  
pp. 096368972199545
Author(s):  
Jun Lu ◽  
Yi Zhang ◽  
Jingjing Sun ◽  
Shulin Huang ◽  
Weizhen Wu ◽  
...  

Immune cell infiltration plays an important role in the pathophysiology of kidney grafts, but the composition of immune cells is ill-defined. Here, we aimed at evaluating the levels and composition of infiltrating immune cells in kidney grafts. We used CIBERSORT, an established algorithm, to estimate the proportions of 22 immune cell types based on gene expression profiles. We found that non-rejecting kidney grafts were characteristic with high rates of M2 macrophages and resting mast cells. The proportion of M1 macrophages and activated NK cells were increased in antibody-mediated rejection (ABMR). In T cell-mediated rejection (TCMR), a significant increase in CD8 T cell and γδT cell infiltration was observed. CD8 positive T cells were dramatically increased in mixed-ABMR/TCMR. Then, the function of ABMR and TCMR prognostic molecular biomarkers were identified. Finally, we described the gene expression of molecular markers for ABMR diagnosis was elevated and related to the ratio of monocytes and M1 macrophages in ABMR biopsies, while the expression of TCMR diagnosis markers was increased too and positively correlated with γδT cells and activated CD4 memory T cells in TCMR biopsies. Our data suggest that CIBERSORT’s deconvolution analysis of gene expression data provides valuable information on the composition of immune cells in renal allografts.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13042-e13042
Author(s):  
Takashi Takeshita ◽  
Li Yan ◽  
Kazuaki Takabe

e13042 Background: Breast cancer (BC) recurrence is largely determined by cancer factors as well as host factors. It has been implicated that infiltrating immune cells play critical roles in long term survival. We hypothesize that immune cell infiltration profile rather than clinical characteristics or gene expression signatures of the primary tumors associate with the timing of cancer recurrence. Methods: 308 primary BCs in TCGA with cancer recurrence data was divided into; recurrence < 2 years (Early, n = 103), 2-5 years (Late, n = 20), and no recurrence > 5 years (Control, n = 185). 1410 primary BCs in METABRIC with BC specific death data was divided into; death < 10 years (Early Death, n = 499), death > 10 years (Late Death, n = 123), and survived > 10 years (Survivors, n = 788). Results: We found that Early tumors demonstrated more aggressive clinical characteristics such as larger tumor, more lymph node metastases, higher pathological grades, higher Stages, and negative estrogen and progesterone receptors, compared with Control tumors. On the other hand, no clinical characteristics of Late tumors were significantly different from Control tumors, which implicate that clinical characteristics cannot distinguish late recurrence from Control. Gene set enrichment analyses revealed that there was no significant gene sets that enriched with Early nor Late recurrence compared with Control, which implicate that gene expression signatures cannot distinguish recurrent tumor from Control. Utilizing CIBERSORT algorithm, we found that M1 was low and M2 was high macrophages in Early compared from Control. Further, anti-cancer lymphocytes, memory CD4 T cells and gamma delta T cells, were significantly lower, and pro-cancerous regulatory T cells were significantly higher in Early and Late compared from Control. In agreement, cytolytic activity score that assess immune cell killing were significantly lower in Early and Late compared from Control. Interestingly, only elevation of regulatory T cells was similar in METABRIC cohort when Early Death and Late Death were compared with Survivors. Conclusions: We found that not clinical characteristics or gene expression signatures, but pro-cancerous immune cells in primary BC associate with cancer recurrence and breast specific death.


Diagnostics ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 171 ◽  
Author(s):  
Ya-Jun Deng ◽  
En-Hui Ren ◽  
Wen-Hua Yuan ◽  
Guang-Zhi Zhang ◽  
Zuo-Long Wu ◽  
...  

This study aimed to find potential diagnostic markers for osteoarthritis (OA) and analyze the role of immune cells infiltration in this pathology. We used OA datasets from the Gene Expression Omnibus database. First, R software was used to identify differentially expressed genes (DEGs) and perform functional correlation analysis. Then least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination algorithms were used to screen and verify the diagnostic markers of OA. Finally, CIBERSORT was used to evaluate the infiltration of immune cells in OA tissues, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. A total of 458 DEGs were screened in this study. GRB10 and E2F3 (AUC = 0.962) were identified as diagnostic markers of OA. Immune cell infiltration analysis found that resting mast cells, T regulatory cells, CD4 memory resting T cells, activated NK cells, and eosinophils may be involved in the OA process. In addition, GRB10 was correlated with NK resting cells, naive CD4 + T cells, and M1 macrophages, while E2F3 was correlated with resting mast cells. In conclusion, GRB10 and E2F3 can be used as diagnostic markers of osteoarthritis, and immune cell infiltration plays an important role in the occurrence and progression of OA.


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