Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis
Over recent years, many researchers have supported the autoimmune theory of sarcoidosis. The presence of uncontrolled inflammatory response on local and system levels in patients with sarcoidosis did not define that the immunoregulatory mechanisms could be affected. The aim of this study was to eval...
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MDPI AG
2023-04-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/13/8/1378 |
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| author | Igor Kudryavtsev Yulia Zinchenko Anna Starshinova Maria Serebriakova Anna Malkova Tatiana Akisheva Dmitriy Kudlay Anzhela Glushkova Piotr Yablonskiy Yehuda Shoenfeld |
| author_facet | Igor Kudryavtsev Yulia Zinchenko Anna Starshinova Maria Serebriakova Anna Malkova Tatiana Akisheva Dmitriy Kudlay Anzhela Glushkova Piotr Yablonskiy Yehuda Shoenfeld |
| author_sort | Igor Kudryavtsev |
| collection | DOAJ |
| description | Over recent years, many researchers have supported the autoimmune theory of sarcoidosis. The presence of uncontrolled inflammatory response on local and system levels in patients with sarcoidosis did not define that the immunoregulatory mechanisms could be affected. The aim of this study was to evaluate the distribution and the disturbance circulating Treg cell subsets in the peripheral blood in patients with sarcoidosis. Materials and methods: A prospective comparative study was performed in 2016–2018 (34 patients with sarcoidosis (men (67.6%), women (32.3%)) were examined). Healthy subjects—the control group (<i>n</i> = 40). The diagnosis of pulmonary sarcoidosis was performed according to the standard criteria. We used two ten-color combinations of antibodies for Treg immunophenotyping. The first one contained CD39–FITC, CD127–PE, CCR4–PE/Dazzle™ 594, CD25–PC5.5, CD161–PC7, CD4–APC, CD8–APC–AF700, CD3–APC/Cy7, HLA–DR–PacBlue, and CD45 RA–BV 510™, while the second consisted of CXCR3–Alexa Fluor 488, CD25–РЕ, CXCR5–РЕ/Dazzle™ 594, CCR4–PerСP/Сy5.5, CCR6–РЕ/Cy7, CD4–АPC, CD8 АPC–AF700, CD3–АPC/Cy7, CCR7–BV 421, and CD45 RA–BV 510. The flow cytometry data were analyzed by using Kaluza software v2.3. A statistical analysis was performed with Statistica 7.0 and GraphPad Prism 8 software packages. Results of the study: Primarily, we found that patients with sarcoidosis had decreased absolute numbers of Treg cells in circulation. We noted that the level of CCR7-expressing Tregs decreased in patients with sarcoidosis vs. the control group (65.55% (60.08; 70.60) vs. 76.93% (69.59; 79.86) with <i>p</i> < 0.001). We noticed that the relative numbers of CD45RA–CCR7+ Tregs decreased in patients with sarcoidosis (27.11% vs. 35.43%, <i>p</i> < 0.001), while the frequency of CD45 RA–CCR7– and CD45RA+ CCR7– Tregs increased compared to the control group (33.3% vs. 22.73% and 0.76% vs. 0.51% with <i>p</i> < 0.001 and <i>p</i> = 0.028, respectively). CXCR3-expressing Treg cell subsets—Th1-like CCR60078CXCR3+ Tregs and Th17.1-like CCR6+ CXCR3+ Tregs—significantly increased in patients with sarcoidosis vs. the control group (14.4% vs. 10.5% with <i>p</i> < 0.01 and 27.9% vs. 22.8% with <i>p</i> < 0.01, respectively). Furthermore, the levels of peripheral blood EM Th17-like Tregs significantly decreased in the sarcoidosis group vs. the control group (36.38% vs. 46.70% with <i>p</i> < 0.001). Finally, we found that CXCR5 expression was increased in CM Tregs cell subsets in patients with sarcoidosis. Conclusions: Our data indicated a decrease in circulating Tregs absolute numbers and several alterations in Treg cell subsets. Moreover, our results highlight the presence of increased levels of CM CXCR5+ follicular Tregs in the periphery that could be linked with the imbalance of follicular Th cell subsets and alterations in B cell, based on the immune response. The balance between the two functionally distinct Treg cell populations—Th1-like and Th17-like Tregs—could be used in sarcoidosis diagnosis and the determination of prognosis and disease outcomes. Furthermore, we want to declare that analysis of Treg numbers of phenotypes could fully characterize their functional activity in peripherally inflamed tissues. |
| first_indexed | 2024-03-11T05:05:43Z |
| format | Article |
| id | doaj.art-2168c8a9e9344a1ba45c27a8bbe1d10d |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-11T05:05:43Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-2168c8a9e9344a1ba45c27a8bbe1d10d2023-11-17T18:54:16ZengMDPI AGDiagnostics2075-44182023-04-01138137810.3390/diagnostics13081378Circulating Regulatory T Cell Subsets in Patients with SarcoidosisIgor Kudryavtsev0Yulia Zinchenko1Anna Starshinova2Maria Serebriakova3Anna Malkova4Tatiana Akisheva5Dmitriy Kudlay6Anzhela Glushkova7Piotr Yablonskiy8Yehuda Shoenfeld9Department of Immunology, Institution of Experimental Medicine, 197376 St. Petersburg, RussiaPhthisiopulmonology Department, St. Petersburg Research Institute of Phthisiopulmonology, 194064 St. Petersburg, RussiaAlmazov National Medical Research Centre, 197341 St. Petersburg, RussiaDepartment of Immunology, Institution of Experimental Medicine, 197376 St. Petersburg, RussiaLaboratory of the Mosaic of Autoimmunity, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of Immunology, Institution of Experimental Medicine, 197376 St. Petersburg, RussiaDepartment of Pharmacology, Sechenov First Moscow State Medical University, 119992 Moscow, RussiaBekhterev National Research Medical Center for Psychiatry and Neurology, 19201 St. Petersburg, RussiaPhthisiopulmonology Department, St. Petersburg Research Institute of Phthisiopulmonology, 194064 St. Petersburg, RussiaLaboratory of the Mosaic of Autoimmunity, St. Petersburg State University, 199034 St. Petersburg, RussiaOver recent years, many researchers have supported the autoimmune theory of sarcoidosis. The presence of uncontrolled inflammatory response on local and system levels in patients with sarcoidosis did not define that the immunoregulatory mechanisms could be affected. The aim of this study was to evaluate the distribution and the disturbance circulating Treg cell subsets in the peripheral blood in patients with sarcoidosis. Materials and methods: A prospective comparative study was performed in 2016–2018 (34 patients with sarcoidosis (men (67.6%), women (32.3%)) were examined). Healthy subjects—the control group (<i>n</i> = 40). The diagnosis of pulmonary sarcoidosis was performed according to the standard criteria. We used two ten-color combinations of antibodies for Treg immunophenotyping. The first one contained CD39–FITC, CD127–PE, CCR4–PE/Dazzle™ 594, CD25–PC5.5, CD161–PC7, CD4–APC, CD8–APC–AF700, CD3–APC/Cy7, HLA–DR–PacBlue, and CD45 RA–BV 510™, while the second consisted of CXCR3–Alexa Fluor 488, CD25–РЕ, CXCR5–РЕ/Dazzle™ 594, CCR4–PerСP/Сy5.5, CCR6–РЕ/Cy7, CD4–АPC, CD8 АPC–AF700, CD3–АPC/Cy7, CCR7–BV 421, and CD45 RA–BV 510. The flow cytometry data were analyzed by using Kaluza software v2.3. A statistical analysis was performed with Statistica 7.0 and GraphPad Prism 8 software packages. Results of the study: Primarily, we found that patients with sarcoidosis had decreased absolute numbers of Treg cells in circulation. We noted that the level of CCR7-expressing Tregs decreased in patients with sarcoidosis vs. the control group (65.55% (60.08; 70.60) vs. 76.93% (69.59; 79.86) with <i>p</i> < 0.001). We noticed that the relative numbers of CD45RA–CCR7+ Tregs decreased in patients with sarcoidosis (27.11% vs. 35.43%, <i>p</i> < 0.001), while the frequency of CD45 RA–CCR7– and CD45RA+ CCR7– Tregs increased compared to the control group (33.3% vs. 22.73% and 0.76% vs. 0.51% with <i>p</i> < 0.001 and <i>p</i> = 0.028, respectively). CXCR3-expressing Treg cell subsets—Th1-like CCR60078CXCR3+ Tregs and Th17.1-like CCR6+ CXCR3+ Tregs—significantly increased in patients with sarcoidosis vs. the control group (14.4% vs. 10.5% with <i>p</i> < 0.01 and 27.9% vs. 22.8% with <i>p</i> < 0.01, respectively). Furthermore, the levels of peripheral blood EM Th17-like Tregs significantly decreased in the sarcoidosis group vs. the control group (36.38% vs. 46.70% with <i>p</i> < 0.001). Finally, we found that CXCR5 expression was increased in CM Tregs cell subsets in patients with sarcoidosis. Conclusions: Our data indicated a decrease in circulating Tregs absolute numbers and several alterations in Treg cell subsets. Moreover, our results highlight the presence of increased levels of CM CXCR5+ follicular Tregs in the periphery that could be linked with the imbalance of follicular Th cell subsets and alterations in B cell, based on the immune response. The balance between the two functionally distinct Treg cell populations—Th1-like and Th17-like Tregs—could be used in sarcoidosis diagnosis and the determination of prognosis and disease outcomes. Furthermore, we want to declare that analysis of Treg numbers of phenotypes could fully characterize their functional activity in peripherally inflamed tissues.https://www.mdpi.com/2075-4418/13/8/1378sarcoidosispathogenesisautoimmunityTregfollicular TregTreg subsets |
| spellingShingle | Igor Kudryavtsev Yulia Zinchenko Anna Starshinova Maria Serebriakova Anna Malkova Tatiana Akisheva Dmitriy Kudlay Anzhela Glushkova Piotr Yablonskiy Yehuda Shoenfeld Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis Diagnostics sarcoidosis pathogenesis autoimmunity Treg follicular Treg Treg subsets |
| title | Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis |
| title_full | Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis |
| title_fullStr | Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis |
| title_full_unstemmed | Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis |
| title_short | Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis |
| title_sort | circulating regulatory t cell subsets in patients with sarcoidosis |
| topic | sarcoidosis pathogenesis autoimmunity Treg follicular Treg Treg subsets |
| url | https://www.mdpi.com/2075-4418/13/8/1378 |
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