Lung CD4+ T-cells in patients with lung fibrosis produce pro-fibrotic interleukin-13 together with interferon-γ

Sikkeland, Liv Ingunn Bjoner; Qiao, Shuo‐Wang; Ueland, Thor; Myrdal, Ole Henrik; Wyrożemski, Łukasz; Aukrust, Pål; Jahnsen, Frode L.; Sjåheim, Tone; Kongerud, Johny; Molberg, Øyvind; Lund, May Brit; Bækkevold, Espen S.

doi:10.1183/13993003.00983-2020

Cited by 11 publications

(10 citation statements)

References 18 publications

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“…Consistent with these earlier findings, patients with progressive fibrosing interstitial lung disease (PF‐ILD) harbored higher levels of IFN‐γ and IL‐13‐double producing CD4 + T cells in BAL compared to controls. Notably, these BAL IL‐13 + /IFN‐γ + CD4 + T cells from PF‐ILD patients exhibited characteristics of conventional T RM cells 130 . In addition to CD4 + T RM cells, lungs from IPF patients also had increased levels of CD103 + CD8 + T RM cells.…”

Section: Trm and Chronic Respiratory Diseasementioning

confidence: 91%

“…Notably, these BAL IL-13 + /IFNγ + CD4 + T cells from PF-ILD patients exhibited characteristics of conventional T RM cells. 130 In addition to CD4 + T RM cells, lungs from IPF patients also had increased levels of CD103 + CD8 + T RM cells. Using scRNAseq, it was recently found that both CD4 + and CD8 + T RM, as well as CD8 + T EM cells, were increased in the lungs of IPF patients.…”

Section: T Rm In Copd and Ipfmentioning

confidence: 92%

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Tissue‐resident memory T cells and lung immunopathology

Cheon

Son

Sun

2023

Immunological Reviews

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Summary Rapid reaction to microbes invading mucosal tissues is key to protect the host against disease. Respiratory tissue‐resident memory T (TRM) cells provide superior immunity against pathogen infection and/or re‐infection, due to their presence at the site of pathogen entry. However, there has been emerging evidence that exuberant TRM‐cell responses contribute to the development of various chronic respiratory conditions including pulmonary sequelae post‐acute viral infections. In this review, we have described the characteristics of respiratory TRM cells and processes underlying their development and maintenance. We have reviewed TRM‐cell protective functions against various respiratory pathogens as well as their pathological activities in chronic lung conditions including post‐viral pulmonary sequelae. Furthermore, we have discussed potential mechanisms regulating the pathological activity of TRM cells and proposed therapeutic strategies to alleviate TRM‐cell‐mediated lung immunopathology. We hope that this review provides insights toward the development of future vaccines or interventions that can harness the superior protective abilities of TRM cells, while minimizing the potential for immunopathology, a particularly important topic in the era of coronavirus disease 2019 (COVID‐19) pandemic.

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Section: Trm and Chronic Respiratory Diseasementioning

confidence: 91%

Section: T Rm In Copd and Ipfmentioning

confidence: 92%

Tissue‐resident memory T cells and lung immunopathology

Cheon

Son

Sun

2023

Immunological Reviews

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“…Twenty-nine patients with IPF [mean age (SD) 66 (7) years, 6 females], and 10 controls [aged 48 (13) years, 7 females] were included in this cross-sectional study and underwent bronchoscopy with BAL ( 5 ). IPF patients were diagnosed according to ATS/ERS criteria after multidisciplinary evaluation ( 6 ).…”

Section: Methodsmentioning

confidence: 99%

A role for the terminal C5-C9 complement pathway in idiopathic pulmonary fibrosis

et al. 2023

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by damage to the alveolar epithelium, leading to fibrosis and excessive accumulation of extracellular matrix in the interstitium of the lung. In the present study we performed high-resolution proteomic profiling of bronchoalveolar lavage (BAL) from IPF patients and controls, and found that the complement pathway was highly upregulated in IPF. The proteins C5, C6, C7, C8, and C9, all of which are part of the complement end product, TCC, were all upregulated. We also found that TCC levels were increased in plasma among IPF patients compared to controls, after adjustment for age, sex and BMI [mean (SD) 0.62 (0.24) vs. 0.33 (0.10), p = 0.031]. These findings suggest a role for the complement system in the pathogenesis of IPF.

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“…PFTs from 577 adult individuals, aged 18-85 years, all of Caucasian ethnicity, were included in the study. The PFTs were obtained from subjects who had participated in recent clinical studies (15,(29)(30)(31)(32)(33) and comprised four different groups (long-term survivors of severe blood disorders, n = 229, pulmonary brosis, n = 148, lung transplantation, n = 88, and healthy, never-smoking controls, n = 112). The clinical studies had all been approved by the hospital's Data Protection O cer and the Regional Committee for Medical and Health Research Ethics.…”

Section: Design and Study Populationmentioning

confidence: 99%

Comparison of different reference values for lung function: implications of inconsistent use among centers

Mangseth

Sikkeland

Durheim

et al. 2023

Preprint

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Background: For interpretation of pulmonary function tests (PFTs), reference values based on sex, age, height and ethnicity are needed. In Norway, the European Coal and Steel Community (ECSC) reference values remain widely used, in spite of recommendations to implement the more recent Global Lung Function Initiative (GLI) reference values. Objective: To assess the effects of changing from ECSC to GLI reference values for spirometry, DLCO and static lung volumes, using a clinical cohort of adults with a broad range in age and lung function. Methods: PFTs from 577 adults (18-85 years, 45% females) included in recent clinical studies were used to compare ECSC and GLI reference values for FVC, FEV1, DLCO, TLC and RV. Percent predicted and lower limit of normal (LLN) were calculated. Bland-Altman plots and paired t-test were used to compare GLI and ECSC predicted values. Results: In both genders, GLI predicted values were lower for FVC and FEV1, and higher for DLCO and RV, compared to ECSC. The disagreement was most pronounced in females, with mean (SD) difference 15 (5) percent points (pp) for DLCO and 17 (9) pp for RV (p<0.001). With GLI, DLCO was below LLN in 23% females, as compared to in 49% with ECSC. Conclusions: The observed differences between GLI and ECSC reference values are likely to entail significant consequences with respect to criteria for diagnostics and treatment, health care benefits and inclusion in clinical trials. To ensure equity of care, the same reference values should be consistently implemented across centers nationwide.

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Lung CD4+ T-cells in patients with lung fibrosis produce pro-fibrotic interleukin-13 together with interferon-γ

Cited by 11 publications

References 18 publications

Tissue‐resident memory T cells and lung immunopathology

Tissue‐resident memory T cells and lung immunopathology

A role for the terminal C5-C9 complement pathway in idiopathic pulmonary fibrosis

Comparison of different reference values for lung function: implications of inconsistent use among centers

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