FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis
RationaleSarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to e...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1301991/full |
| _version_ | 1797384863006851072 |
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| author | Karen C. Patterson Wallace T. Miller Wayne W. Hancock Tatiana Akimova |
| author_facet | Karen C. Patterson Wallace T. Miller Wayne W. Hancock Tatiana Akimova |
| author_sort | Karen C. Patterson |
| collection | DOAJ |
| description | RationaleSarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to evaluate the association of disease course and immune responses in pulmonary sarcoidosis.MethodsIn this prospective cohort study of 30 subjects, most of whom were followed for one year, we evaluated 14 inflammatory markers in plasma, 13 Treg/T cell flow cytometry markers and 8 parameters of FOXP3+ Treg biology, including suppressive function, epigenetic features and stability.ResultsWe identified a set of 13 immunological parameters that differ in sarcoidosis subjects in comparison with healthy donors. Five of those were inversely correlated with suppressive function of Tregs in sarcoidosis, and six (TNFα, TNFR I and II, sCD25, Ki-67 and number of Tregs) were particularly upregulated or increased in subjects with thoracic lymphadenopathy. Treg suppressive function was significantly lower in patients with thoracic lymphadenopathy, and in patients with higher burdens of pulmonary and systemic symptoms. A combination of five inflammatory markers, Ki-67 expression, Treg function, and lung diffusion capacity evaluated at study entry predicted need for therapy at one year follow-up in 90% of cases.ConclusionTregs may suppress ongoing inflammation at local and systemic levels, and TNFα, TNFR I and II, sCD25 and Ki-67 emerge as attractive biomarkers for in vivo sarcoid inflammatory activity. |
| first_indexed | 2024-03-08T21:45:37Z |
| format | Article |
| id | doaj.art-0cc69c9fb4d74a2996c9ab15a543d054 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T21:45:37Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0cc69c9fb4d74a2996c9ab15a543d0542023-12-20T09:05:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.13019911301991FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosisKaren C. Patterson0Wallace T. Miller1Wayne W. Hancock2Tatiana Akimova3Division of Pulmonary, Allergy, and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDivision of Transplant Immunology, Department of Pathology and Laboratory Medicine, and Biesecker Center for Pediatric Liver Diseases, Children’s Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDivision of Transplant Immunology, Department of Pathology and Laboratory Medicine, and Biesecker Center for Pediatric Liver Diseases, Children’s Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesRationaleSarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to evaluate the association of disease course and immune responses in pulmonary sarcoidosis.MethodsIn this prospective cohort study of 30 subjects, most of whom were followed for one year, we evaluated 14 inflammatory markers in plasma, 13 Treg/T cell flow cytometry markers and 8 parameters of FOXP3+ Treg biology, including suppressive function, epigenetic features and stability.ResultsWe identified a set of 13 immunological parameters that differ in sarcoidosis subjects in comparison with healthy donors. Five of those were inversely correlated with suppressive function of Tregs in sarcoidosis, and six (TNFα, TNFR I and II, sCD25, Ki-67 and number of Tregs) were particularly upregulated or increased in subjects with thoracic lymphadenopathy. Treg suppressive function was significantly lower in patients with thoracic lymphadenopathy, and in patients with higher burdens of pulmonary and systemic symptoms. A combination of five inflammatory markers, Ki-67 expression, Treg function, and lung diffusion capacity evaluated at study entry predicted need for therapy at one year follow-up in 90% of cases.ConclusionTregs may suppress ongoing inflammation at local and systemic levels, and TNFα, TNFR I and II, sCD25 and Ki-67 emerge as attractive biomarkers for in vivo sarcoid inflammatory activity.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1301991/fullregulatory T-cellsTregsarcoidosissCD25Ki-67TNFRI |
| spellingShingle | Karen C. Patterson Wallace T. Miller Wayne W. Hancock Tatiana Akimova FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis Frontiers in Immunology regulatory T-cells Treg sarcoidosis sCD25 Ki-67 TNFRI |
| title | FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis |
| title_full | FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis |
| title_fullStr | FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis |
| title_full_unstemmed | FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis |
| title_short | FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis |
| title_sort | foxp3 regulatory t cells are associated with the severity and prognosis of sarcoidosis |
| topic | regulatory T-cells Treg sarcoidosis sCD25 Ki-67 TNFRI |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1301991/full |
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