ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Reversal of global CD4+ subset dysfunction is associated with spontaneous clinical resolution of pulmonary sarcoidosis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Declining Pulmonary Function in Interstitial Lung Disease Linked to Lymphocyte Dysfunction.American journal of respiratory and critical care medicine · 2020Pooled it
- Mycobacterium tuberculosis-specific blood immune signatures distinguish sarcoidosis from tuberculosis disease.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Immunopathogenesis of Sarcoidosis.Seminars in respiratory and critical care medicine · 2025Review
- Korean Guidelines for the Diagnosis and Management of Interstitial Lung Diseases: Sarcoidosis.Tuberculosis and respiratory diseases · 2025Article
- Fibrotic Pulmonary Sarcoidosis-From Pathogenesis to Management.Journal of clinical medicine · 2025Review
- Sarcoidosis: molecular mechanisms and therapeutic strategies.Molecular biomedicine · 2025Review
- Phenotypes and Endotypes in Sarcoidosis: Unraveling Prognosis and Disease Course.Biomedicines · 2025Review
- Increased proportions of circulating PD-1Respiratory research · 2024Article
- Coexistent sarcoidosis mimics metastasis in a patient with early-stage non-small cell lung cancer: a case report.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2024Article
- Clinical Manifestations and Management of Fibrotic Pulmonary Sarcoidosis.Journal of clinical medicine · 2023Review
- Lymphopenia and high Ki-67 expression in peripheral blood CD4+ and CD8+ T cells associate with progressive sarcoidosis.BMJ open respiratory research · 2023Article
- Pulmonary Sarcoidosis and Immune Dysregulation: A Pilot Study on Possible Correlation.Diagnostics (Basel, Switzerland) · 2023Article
- Cardiac Sarcoidosis: A Literature Review of Current Recommendations on Diagnosis and Management.Cureus · 2023Review
- Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model.Experimental and therapeutic medicine · 2023Article
- Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis.Diagnostics (Basel, Switzerland) · 2023Article
- Acthar Gel Inhibits the Activation of CD4Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- Role of Serum Soluble Interleukin-2 Receptor Level in the Diagnosis of Sarcoidosis: A Systematic Review and Meta-Analysis.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2023Article
- Th17/Treg Imbalance: Implications in Lung Inflammatory Diseases.International journal of molecular sciences · 2023Review
- Cardiac sarcoidosis: a comprehensive review of risk factors, pathogenesis, diagnosis, clinical manifestations, and treatment strategies.Frontiers in cardiovascular medicine · 2023Review
- Immune-mediated lung diseases: A narrative review.Frontiers in medicine · 2023Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Sarcoidosis pathogenesis is characterized by peripheral anergy and an exaggerated, pulmonary CD4(+) Th1 response. In this study, we demonstrate that CD4(+) anergic responses to polyclonal TCR stimulation are present peripherally and within the lungs of sarcoid patients. Consistent with prior observations, spontaneous release of IL-2 was noted in sarcoidosis bronchoalveolar lavage CD4(+) T cells. However, in contrast to spontaneous hyperactive responses reported previously, the cells displayed anergic responses to polyclonal TCR stimulation. The anergic responses correlated with diminished expression of the Src kinase Lck, protein kinase C-θ, and NF-κB, key mediators of IL-2 transcription. Although T regulatory (Treg) cells were increased in sarcoid patients, Treg depletion from the CD4(+) T cell population of sarcoidosis patients did not rescue IL-2 and IFN-γ production, whereas restoration of the IL-2 signaling cascade, via protein kinase C-θ overexpression, did. Furthermore, sarcoidosis Treg cells displayed poor suppressive capacity indicating that T cell dysfunction was a global CD4(+) manifestation. Analyses of patients with spontaneous clinical resolution revealed that restoration of CD4(+) Th1 and Treg cell function was associated with resolution. Conversely, disease progression exhibited decreased Th1 cytokine secretion and proliferative capacity, and reduced Lck expression. These findings implicate normalized CD4(+) T cell function as a potential therapeutic target for sarcoidosis resolution.
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