Cargando…
PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis
Sarcoidosis is a granulomatous diseases affecting the lungs. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a histologically granulomatous B-mediated disorder characterized by activated T cells. The expression of immune checkpoint (IC) molecules (PD1, CTLA4, TIGIT) on T-...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820065/ https://www.ncbi.nlm.nih.gov/pubmed/36613701 http://dx.doi.org/10.3390/ijms24010256 |
_version_ | 1784865379564126208 |
---|---|
author | d’Alessandro, Miriana Conticini, Edoardo Bergantini, Laura Mezzasalma, Fabrizio Cameli, Paolo Baglioni, Stefano Armati, Martina Abbritti, Marta Bargagli, Elena |
author_facet | d’Alessandro, Miriana Conticini, Edoardo Bergantini, Laura Mezzasalma, Fabrizio Cameli, Paolo Baglioni, Stefano Armati, Martina Abbritti, Marta Bargagli, Elena |
author_sort | d’Alessandro, Miriana |
collection | PubMed |
description | Sarcoidosis is a granulomatous diseases affecting the lungs. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a histologically granulomatous B-mediated disorder characterized by activated T cells. The expression of immune checkpoint (IC) molecules (PD1, CTLA4, TIGIT) on T- and NK-cells negatively regulate the T-cell immune function. The present study aimed to explore the peripheral distribution of IC molecules to better elucidate their peripheral tolerance failure, which might reflect the development of diseases. Patients referred to Respiratory Diseases and Rheumatology Unit of Siena University Hospital were prospectively and consecutively enrolled. Healthy subjects were also enrolled as a control group. Multicolor flow cytometric analysis was performed to detect IC molecules in the peripheral blood of patients. Twenty-three patients were consecutively and prospectively enrolled in the study: 11 patients had an AAV diagnosis and 12 had sarcoidosis. CD4(+)PD1(+) cells were higher in sarcoidosis and GPA than in HC (p = 0.0250 and p = 0.0253, respectively). CD56(+)CTLA4(+) were higher in sarcoidosis than GPA, MPA and HC (p = 0.0085, p = 0.0042 and p = 0.0004, respectively). CTLA4(+)NK cells clustered for 100% of sarcoidosis patients according to decision tree analysis, while PD1(+)CD4 and CD8 cells for clustered for 100% of GPA patients. Our analyses showed substantial differences between sarcoidosis and AAV, further confirming the immunological peculiarity of this disease. Despite these advances, the pathogenesis remains incompletely understood, indicating an urgent need for further research to reveal the distinct immunological events in this process, with the hope to open up new therapeutic avenues and, if possible, to develop preventive measures. |
format | Online Article Text |
id | pubmed-9820065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98200652023-01-07 PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis d’Alessandro, Miriana Conticini, Edoardo Bergantini, Laura Mezzasalma, Fabrizio Cameli, Paolo Baglioni, Stefano Armati, Martina Abbritti, Marta Bargagli, Elena Int J Mol Sci Article Sarcoidosis is a granulomatous diseases affecting the lungs. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a histologically granulomatous B-mediated disorder characterized by activated T cells. The expression of immune checkpoint (IC) molecules (PD1, CTLA4, TIGIT) on T- and NK-cells negatively regulate the T-cell immune function. The present study aimed to explore the peripheral distribution of IC molecules to better elucidate their peripheral tolerance failure, which might reflect the development of diseases. Patients referred to Respiratory Diseases and Rheumatology Unit of Siena University Hospital were prospectively and consecutively enrolled. Healthy subjects were also enrolled as a control group. Multicolor flow cytometric analysis was performed to detect IC molecules in the peripheral blood of patients. Twenty-three patients were consecutively and prospectively enrolled in the study: 11 patients had an AAV diagnosis and 12 had sarcoidosis. CD4(+)PD1(+) cells were higher in sarcoidosis and GPA than in HC (p = 0.0250 and p = 0.0253, respectively). CD56(+)CTLA4(+) were higher in sarcoidosis than GPA, MPA and HC (p = 0.0085, p = 0.0042 and p = 0.0004, respectively). CTLA4(+)NK cells clustered for 100% of sarcoidosis patients according to decision tree analysis, while PD1(+)CD4 and CD8 cells for clustered for 100% of GPA patients. Our analyses showed substantial differences between sarcoidosis and AAV, further confirming the immunological peculiarity of this disease. Despite these advances, the pathogenesis remains incompletely understood, indicating an urgent need for further research to reveal the distinct immunological events in this process, with the hope to open up new therapeutic avenues and, if possible, to develop preventive measures. MDPI 2022-12-23 /pmc/articles/PMC9820065/ /pubmed/36613701 http://dx.doi.org/10.3390/ijms24010256 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article d’Alessandro, Miriana Conticini, Edoardo Bergantini, Laura Mezzasalma, Fabrizio Cameli, Paolo Baglioni, Stefano Armati, Martina Abbritti, Marta Bargagli, Elena PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
title | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
title_full | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
title_fullStr | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
title_full_unstemmed | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
title_short | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
title_sort | pd1, ctla4 and tigit expression on t and nk cells in granulomatous diseases: sarcoidosis and anca-associated vasculitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820065/ https://www.ncbi.nlm.nih.gov/pubmed/36613701 http://dx.doi.org/10.3390/ijms24010256 |
work_keys_str_mv | AT dalessandromiriana pd1ctla4andtigitexpressionontandnkcellsingranulomatousdiseasessarcoidosisandancaassociatedvasculitis AT conticiniedoardo pd1ctla4andtigitexpressionontandnkcellsingranulomatousdiseasessarcoidosisandancaassociatedvasculitis AT bergantinilaura pd1ctla4andtigitexpressionontandnkcellsingranulomatousdiseasessarcoidosisandancaassociatedvasculitis AT mezzasalmafabrizio pd1ctla4andtigitexpressionontandnkcellsingranulomatousdiseasessarcoidosisandancaassociatedvasculitis AT camelipaolo pd1ctla4andtigitexpressionontandnkcellsingranulomatousdiseasessarcoidosisandancaassociatedvasculitis AT baglionistefano pd1ctla4andtigitexpressionontandnkcellsingranulomatousdiseasessarcoidosisandancaassociatedvasculitis AT armatimartina pd1ctla4andtigitexpressionontandnkcellsingranulomatousdiseasessarcoidosisandancaassociatedvasculitis AT abbrittimarta pd1ctla4andtigitexpressionontandnkcellsingranulomatousdiseasessarcoidosisandancaassociatedvasculitis AT bargaglielena pd1ctla4andtigitexpressionontandnkcellsingranulomatousdiseasessarcoidosisandancaassociatedvasculitis |