CD103 Expression on Regulatory and Follicular T Cells in Lymph Nodes, Bronchoalveolar Lavage Fluid and Peripheral Blood of Sarcoidosis Patients

d’Alessandro, Miriana; Gangi, Sara; Cavallaro, Dalila; Bergantini, Laura; Mezzasalma, Fabrizio; Cattelan, Stefano; Baglioni, Stefano; Abbritti, Marta; Cameli, Paolo; Bargagli, Elena

doi:10.3390/life12050762

Cited by 7 publications

(12 citation statements)

References 41 publications

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“…Moreover, CD8+CD103+ may be involved in the autoimmune process [47]. However, it should be noted that there is an imbalance in circulating, alveolar and lymph node CD8+CD103+ T cells in the development of sarcoidosis [48]. Similar to the CD31+ marker, it seems that our results regarding the possible prognostic role of the CD8+CD103+ marker are in indirect agreement with the results of other authors.…”

Section: Discussionsupporting

confidence: 90%

Lymphocyte Subsets and Pulmonary Nodules to Predict the Progression of Sarcoidosis

et al. 2023

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The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis, remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. A 2-year follow-up of the study population after the initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF) and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was performed. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes)—blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.

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Section: Discussionsupporting

confidence: 90%

Lymphocyte Subsets and Pulmonary Nodules to Predict the Progression of Sarcoidosis

et al. 2023

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“…Moreover, CD8+CD103+ may be involved in the autoimmune process [43]. However, it should be noted that there is an imbalance in circulating, alveolar, and lymph node CD8+CD103+ T cells in the development of sarcoidosis [44]. Similar to the CD31+ marker, it seems that our results regarding the possible prognostic role of the CD8+CD103+ marker are in indirect agreement with the results of other authors.…”

Section: Discussionsupporting

confidence: 90%

CD4+CD31+ and CD4+CD44+ Lymphocytes in Peripheral Blood, CD8+CD31+ and CD8+CD103+ Lymphocytes in Bronchoalveolar Lavage Fluid, and Pulmonary Nodules in Predicting the Course of Pulmonary Sarcoidosis

Danila¹,

Aleksonienė²,

Besusparis³

et al. 2023

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The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. 2 years follow-up of the study population after initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF), and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was done. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes) – blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity, and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.

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“…Importantly, Th1-, Th17-, and Th17.1-like Tregs phenotypically mimicked conventional IFN-γ and IL-17-producting Th cells and expressed similar patterns of ‘homing’ molecules [ 46 , 73 ], including chemokine receptors that regulated Treg cell migration to the sites of inflammation [ 74 , 75 ]. It is known that circulating and BAL-associated CD4+ T cells that produce IFN-γ play an important role in sarcoidosis-associated inflammation and granuloma formation, just as serum and BAL from patients with sarcoidosis are characterized by the increased levels of IFN-γ [ 76 , 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, Duhen et al suggested that the increased frequency of IFN-γ-producing Treg cells in patients with type-1 diabetes and multiple sclerosis could be a response to autoimmune inflammation in these patients [ 45 ]. Next, E.L. McClymont et al reported that FOXP3+ IFNγ+ Treg frequency was significantly increased in patients with type 1 diabetes compared to the control group [ 73 ]. Similarly, an effector memory Treg subset expressing HLA-DR, CCR4, CCR6, CXCR3, and GATA3 was increased in the high-risk group of patients with type 1 diabetes [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis

et al. 2023

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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 (n = 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 p < 0.001). We noticed that the relative numbers of CD45RA–CCR7+ Tregs decreased in patients with sarcoidosis (27.11% vs. 35.43%, p < 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 p < 0.001 and p = 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 p < 0.01 and 27.9% vs. 22.8% with p < 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 p < 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.

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CD103 Expression on Regulatory and Follicular T Cells in Lymph Nodes, Bronchoalveolar Lavage Fluid and Peripheral Blood of Sarcoidosis Patients

Cited by 7 publications

References 41 publications

Lymphocyte Subsets and Pulmonary Nodules to Predict the Progression of Sarcoidosis

Lymphocyte Subsets and Pulmonary Nodules to Predict the Progression of Sarcoidosis

CD4+CD31+ and CD4+CD44+ Lymphocytes in Peripheral Blood, CD8+CD31+ and CD8+CD103+ Lymphocytes in Bronchoalveolar Lavage Fluid, and Pulmonary Nodules in Predicting the Course of Pulmonary Sarcoidosis

Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis

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