Immune and barrier characterization of atopic dermatitis skin phenotype in Tanzanian patients

Lang, Claudia; Renert‐Yuval, Yael; Duca, Ester Del; Pavel, Ana B.; Wu, Jianni; Zhang, Ning; Dubin, Celina; Obi, Ashley; Chowdhoury, Mashkura; Kim, Madeline; Estrada, Yeriel; Krueger, James G.; Kaderbhai, H.; Semango, George; Schmid‐Grendelmeier, Peter; Brüggen, Marie‐Charlotte; Masenga, John; Guttman‐Yassky, Emma

doi:10.1016/j.anai.2021.04.023

Cited by 27 publications

(34 citation statements)

References 63 publications

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“…CXCL10 exhibits chemotactic activity toward activated T lymphocytes and monocytes in the peripheral blood and is produced by activated T cells, monocytes, endothelial cells, and keratinocytes (Qi et al, 2009). In AD patients, the serum levels of CXCL10 and the expression levels of CXCL10 in skin lesions were significantly increased in comparison to the levels observed in HCs (Esaki et al, 2016;Brunner et al, 2017;Lang et al, 2021). This is consistent with our findings.…”

Section: Discussionsupporting

confidence: 91%

Identification of Effective Diagnostic Biomarkers and Immune Cell Infiltration in Atopic Dermatitis by Comprehensive Bioinformatics Analysis

Han

2022

Front. Mol. Biosci.

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Background: Atopic dermatitis (AD) is a dermatological disorder characterized by symptoms such as chronically inflamed skin and frequently intolerable itching. The mechanism underlying AD development is still unclear. Our study aims to identify the diagnostic and therapeutic biomarkers for AD and provide insight into immune mechanisms at the molecular level through bioinformatics analysis.Methods: The GSE6012, GSE32924, and GSE36842 gene expression profiles were obtained for analysis from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were segregated using the “Batch correction” and “RobustRankAggreg” methods. Weighted gene co-expression network analysis (WGCNA) was performed to screen for module genes with AD traits. Then, common DEGs (co-DEGs) were screened out via combined differential expression analysis and WGCNA. Functional enrichment analysis was performed for these co-DEGs using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), followed by protein-protein interaction network analysis. Candidate hub genes were identified using the “cytoHubba” plugin in Cytoscape, and their value for AD diagnosis was validated using receiver operating characteristic curve analysis in the external database GSE120721. Immunohistochemical staining was performed for further validation. The CIBERSORT algorithm was used to evaluate skin samples obtained from healthy controls (HCs) and lesions of AD patients, to determine the extent of immune cell infiltration. The association between the identified hub genes and significant differential immune cells was analyzed using Pearson correlation analysis.Results: A total of 259 DEGs were acquired from the intersection of DEGs obtained by the two independent procedures, and 331 AD-trait module genes were separated out from the blue module via WGCNA analysis. Then, 169 co-DEGs arising from the intersection of the 259 DEGs and the 331 AD-trait module genes were obtained. We found that co-DEGs were significantly enhanced in the type I interferon and IL-17 signal transduction pathways. Thirteen potential hub genes were identified using Cytoscape. Five hub genes (CCR7, CXCL10, IRF7, MMP1, and RRM2) were identified after screening via external dataset validation and immunohistochemical analysis. We also identified four significant differential immune cells, i.e., activated dendritic cells, plasma cells, resting mast cells, and CD4+ naïve T cells, between AD patients and HCs. Moreover, the relationship between the identified hub genes and significant differential immune cells was analyzed. The results showed that the CCR7 expression level was positively correlated with the number of CD4+ naïve T cells (R = 0.42, p = 0.011).Conclusion: CCR7, CXCL10, IRF7, MMP1, and RRM2 could be potential diagnostic and therapeutic biomarkers for AD. CCR7 expression level was positively correlated with the number of CD4+ naïve T cells in AD. These findings need to be corroborated in future studies.

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Section: Discussionsupporting

confidence: 91%

Identification of Effective Diagnostic Biomarkers and Immune Cell Infiltration in Atopic Dermatitis by Comprehensive Bioinformatics Analysis

Han

2022

Front. Mol. Biosci.

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“…The immune cells infiltrations also vary among different AD ethnicities. African American AD patients ( 172 ), Tanzanian AD patients ( 173 ), and Asian AD patients ( 174 , 175 ) had higher Th2/Th22 skewing than European Americans. Although common Th2/Th22 skewing can be found in different age groups ( 176 ), adult AD patients had elevated IL-22 frequencies than infants and adolescents ( 177 , 178 ) but decreased with age in elderly AD patients especially those over 40 ( 179 , 180 ).…”

Section: The Roles Of Th22 Cells In Skin Diseasesmentioning

confidence: 98%

The Role of T Helper 22 Cells in Dermatological Disorders

Pan

Wang

et al. 2022

Front. Immunol.

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T helper 22 (Th22) cells are a newly identified subset of CD4+ T cells that secrete the effector cytokine interleukin 22 (IL-22) upon specific antigen stimulation, barely with IFN-γ or IL-17. Increasing studies have demonstrated that Th22 cells and IL-22 play essential roles in skin barrier defense and skin disease pathogenesis since the IL-22 receptor is widely expressed in the skin, especially in keratinocytes. Herein, we reviewed the characterization, differentiation, and biological activities of Th22 cells and elucidated their roles in skin health and disease. We mainly focused on the intricate crosstalk between Th22 cells and keratinocytes and provided potential therapeutic strategies targeting the Th22/IL-22 signaling pathway.

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“…CCL-17, CCL-18, and CCL-22, all dendrocyte-activated chemokines, are differentially pronounced in AD (43,54,64,83,115,(129)(130)(131)(132). Interestingly, IL-4 activates different antigen-presenting cells, contributing to this observation.…”

Section: Interleukin-4mentioning

confidence: 98%

The role of cytokines in atopic dermatitis: a breakthrough in immunopathogenesis and treatment

Alsabbagh¹,

Ismaeel²

2022

Acta Dermatovenerologica Alpina Pannonica Et Adriatica

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Atopic dermatitis is a multifactorial inflammatory skin disease with a complex immunopathogenesis that is characterized by an underlying imbalance of T-cell subsets. Although cytokines of type 2 immunity consistently predominate in the acute phase of atopic dermatitis, there is strong evidence supporting the contribution of cytokines of type 1 immunity, type 3 immunity, and other cytokines in the development and progression of the disease. This review explores the cytokine network in atopic dermatitis, and it highlights areas and causes of controversy in the immunopathogenesis of the disease. In addition, it presents the current therapeutic targets currently being investigated, including monoclonal antibodies and small molecules that inhibit cytokines and downstream signaling molecules in atopic dermatitis. We conclude that atopic dermatitis has a complex and controversial cytokine profile. Understanding the role of cytokines in the immunopathogenesis of the disease is essential for identifying personalized targets for better management and disease control.

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Immune and barrier characterization of atopic dermatitis skin phenotype in Tanzanian patients

Cited by 27 publications

References 63 publications

Identification of Effective Diagnostic Biomarkers and Immune Cell Infiltration in Atopic Dermatitis by Comprehensive Bioinformatics Analysis

Identification of Effective Diagnostic Biomarkers and Immune Cell Infiltration in Atopic Dermatitis by Comprehensive Bioinformatics Analysis

The Role of T Helper 22 Cells in Dermatological Disorders

The role of cytokines in atopic dermatitis: a breakthrough in immunopathogenesis and treatment

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