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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-...

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Autores principales: d’Alessandro, Miriana, Conticini, Edoardo, Bergantini, Laura, Mezzasalma, Fabrizio, Cameli, Paolo, Baglioni, Stefano, Armati, Martina, Abbritti, Marta, Bargagli, Elena
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
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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.
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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
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