Systemic Sclerosis Perturbs the Architecture of the Immunome
Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive fibrosis of skin and internal organs, and vascular dysfunction. Association of T and B cell subsets has been reported in SSc; however, there is lack of systematic studies of functional relations between immune cell subsets...
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doaj-baeaeda97260400cb3eb74c553eaec1e2020-11-25T03:36:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-08-011110.3389/fimmu.2020.01602537760Systemic Sclerosis Perturbs the Architecture of the ImmunomeBhairav Paleja0Andrea Hsiu Ling Low1Andrea Hsiu Ling Low2Pavanish Kumar3Suzan Saidin4Ahmad Lajam5Sharifah Nur Hazirah6Camillus Chua7Lai Li Yun8Salvatore Albani9Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore, SingaporeDepartment of Rheumatology and Immunology, Singapore General Hospital, Singapore, SingaporeDuke-NUS Medical School, Singapore, SingaporeTranslational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore, SingaporeTranslational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore, SingaporeTranslational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore, SingaporeTranslational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore, SingaporeTranslational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore, SingaporeTranslational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore, SingaporeTranslational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore, SingaporeSystemic sclerosis (SSc) is an autoimmune disease characterized by excessive fibrosis of skin and internal organs, and vascular dysfunction. Association of T and B cell subsets has been reported in SSc; however, there is lack of systematic studies of functional relations between immune cell subsets in this disease. This lack of mechanistic knowledge hampers targeted intervention. In the current study we sought to determine differential immune cell composition and their interactions in peripheral blood of SSc patients. Mononuclear cells from blood of SSc patients (n = 20) and healthy controls (n = 10) were analyzed by mass cytometry using a 36-marker (cell surface and intracellular) panel. Transcriptome analysis (m-RNA sequencing) was performed on sorted T and B cell subsets. Unsupervised clustering analysis revealed significant differences in the frequencies of T and B cell subsets in patients. Correlation network analysis highlighted an overall dysregulated immune architecture coupled with domination of inflammatory senescent T cell modules in SSc patients. Transcriptome analysis of sorted immune cells revealed an activated phenotype of CD4 and mucosal associated invariant T (MAIT) cells in patients, accompanied by increased expression of inhibitory molecules, reminiscent of phenotype exhibited by functionally adapted, exhausted T cells in response to chronic stimulation. Overall, this study provides an in-depth analysis of the systemic immunome in SSc, highlighting the potential pathogenic role of inflammation and chronic stimulation-mediated “functional adaptation” of immune cells.https://www.frontiersin.org/article/10.3389/fimmu.2020.01602/fullsystemic sclerosisMAITmass cytometryimmunomechronic stimulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bhairav Paleja Andrea Hsiu Ling Low Andrea Hsiu Ling Low Pavanish Kumar Suzan Saidin Ahmad Lajam Sharifah Nur Hazirah Camillus Chua Lai Li Yun Salvatore Albani |
spellingShingle |
Bhairav Paleja Andrea Hsiu Ling Low Andrea Hsiu Ling Low Pavanish Kumar Suzan Saidin Ahmad Lajam Sharifah Nur Hazirah Camillus Chua Lai Li Yun Salvatore Albani Systemic Sclerosis Perturbs the Architecture of the Immunome Frontiers in Immunology systemic sclerosis MAIT mass cytometry immunome chronic stimulation |
author_facet |
Bhairav Paleja Andrea Hsiu Ling Low Andrea Hsiu Ling Low Pavanish Kumar Suzan Saidin Ahmad Lajam Sharifah Nur Hazirah Camillus Chua Lai Li Yun Salvatore Albani |
author_sort |
Bhairav Paleja |
title |
Systemic Sclerosis Perturbs the Architecture of the Immunome |
title_short |
Systemic Sclerosis Perturbs the Architecture of the Immunome |
title_full |
Systemic Sclerosis Perturbs the Architecture of the Immunome |
title_fullStr |
Systemic Sclerosis Perturbs the Architecture of the Immunome |
title_full_unstemmed |
Systemic Sclerosis Perturbs the Architecture of the Immunome |
title_sort |
systemic sclerosis perturbs the architecture of the immunome |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-08-01 |
description |
Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive fibrosis of skin and internal organs, and vascular dysfunction. Association of T and B cell subsets has been reported in SSc; however, there is lack of systematic studies of functional relations between immune cell subsets in this disease. This lack of mechanistic knowledge hampers targeted intervention. In the current study we sought to determine differential immune cell composition and their interactions in peripheral blood of SSc patients. Mononuclear cells from blood of SSc patients (n = 20) and healthy controls (n = 10) were analyzed by mass cytometry using a 36-marker (cell surface and intracellular) panel. Transcriptome analysis (m-RNA sequencing) was performed on sorted T and B cell subsets. Unsupervised clustering analysis revealed significant differences in the frequencies of T and B cell subsets in patients. Correlation network analysis highlighted an overall dysregulated immune architecture coupled with domination of inflammatory senescent T cell modules in SSc patients. Transcriptome analysis of sorted immune cells revealed an activated phenotype of CD4 and mucosal associated invariant T (MAIT) cells in patients, accompanied by increased expression of inhibitory molecules, reminiscent of phenotype exhibited by functionally adapted, exhausted T cells in response to chronic stimulation. Overall, this study provides an in-depth analysis of the systemic immunome in SSc, highlighting the potential pathogenic role of inflammation and chronic stimulation-mediated “functional adaptation” of immune cells. |
topic |
systemic sclerosis MAIT mass cytometry immunome chronic stimulation |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.01602/full |
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