Increased Interleukin-17 and Glucocorticoid Receptor-β Expression in Interstitial Lung Diseases and Corticosteroid Insensitivity

Lo, Chun‐Yu; Wang, Chunhua; Wang, Chih‐Wei; Chen, Chih‐Jung; Huang, Hung‐Yu; Chung, Fu‐Tsai; Huang, Yu‐Chen; Lin, Changwei; Lee, Chung-Shu; Lin, Chun‐Yu; Lin, Chiao-Yun; Chang, Po‐Jui; Lin, Ting-Yu; Heh, Chih-Chen; He, Jung-Ru; Chung, Kian Fan

doi:10.3389/fimmu.2022.905727

Cited by 9 publications

(10 citation statements)

References 49 publications

(66 reference statements)

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“…Infiltration of lung tissue by Th17 lymphocytes and their production of cytokines in a mouse model of severe asthma was enhanced by GCs [9], which confirms the role of Th17 cells in GC-resistant inflammatory conditions such as asthma [156]. In difficult-to-treat asthma in humans, an increase in Th17 cytokines causes the upregulation of glucocorticoid receptor-beta (GR-β) [157,158], contributing to the dysregulation of the GRα/GRβ ratio [159] and disrupting GC binding to GR and its translocation to the nucleus.…”

Section: Glucocorticoid Resistance and Th17 Lymphocytesmentioning

confidence: 63%

Th17 Cells, Glucocorticoid Resistance, and Depression

Khantakova,

Mutovina,

Ayriyants

et al. 2023

Cells

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Depression is a severe mental disorder that disrupts mood and social behavior and is one of the most common neuropsychological symptoms of other somatic diseases. During the study of the disease, a number of theories were put forward (monoamine, inflammatory, vascular theories, etc.), but none of those theories fully explain the pathogenesis of the disease. Steroid resistance is a characteristic feature of depression and can affect not only brain cells but also immune cells. T-helper cells 17 type (Th17) are known for their resistance to the inhibitory effects of glucocorticoids. Unlike the inhibitory effect on other subpopulations of T-helper cells, glucocorticoids can enhance the differentiation of Th17 lymphocytes, their migration to the inflammation, and the production of IL-17A, IL-21, and IL-23 in GC-resistant disease. According to the latest data, in depression, especially the treatment-resistant type, the number of Th17 cells in the blood and the production of IL-17A is increased, which correlates with the severity of the disease. However, there is still a significant gap in knowledge regarding the exact mechanisms by which Th17 cells can influence neuroinflammation in depression. In this review, we discuss the mutual effect of glucocorticoid resistance and Th17 lymphocytes on the pathogenesis of depression.

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Section: Glucocorticoid Resistance and Th17 Lymphocytesmentioning

confidence: 63%

Th17 Cells, Glucocorticoid Resistance, and Depression

Khantakova,

Mutovina,

Ayriyants

et al. 2023

Cells

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“…TNFRSF17 immunoreactivity was quantified in three randomly selected representative slide areas (×400 magnification) using a light microscope. The percentage of TNFRSF17-positive area out of the total area was calculated (23,24,(26)(27)(28).…”

Section: Immunohistochemistry Stainingmentioning

confidence: 99%

Uncovering lupus nephritis-specific genes and the potential of TNFRSF17-targeted immunotherapy: a high-throughput sequencing study

Zou,

Yang,

et al. 2024

Front. Immunol.

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IntroductionLupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets.MethodsWe performed high-throughput transcriptome sequencing on peripheral blood mononuclear cells (PBMCs) from LN patients. Healthy individuals and SLE patients without LN were used as controls. To validate the sequencing results, qRT-PCR was performed for 5 upregulated and 5 downregulated genes. Furthermore, the effect of the TNFRSF17-targeting drug IBI379 on patient plasma cells and B cells was evaluated by flow cytometry.ResultsOur analysis identified 1493 and 205 differential genes in the LN group compared to the control and SLE without LN groups respectively, with 70 genes common to both sets, marking them as LN-specific. These LN-specific genes were significantly enriched in the ‘regulation of biological quality’ GO term and the cell cycle pathway. Notably, several genes including TNFRSF17 were significantly overexpressed in the kidneys of both LN patients and NZB/W mice. TNFRSF17 levels correlated positively with urinary protein levels, and negatively with complement C3 and C4 levels in LN patients. The TNFRSF17-targeting drug IBI379 effectively induced apoptosis in patient plasma cells without significantly affecting B cells.DiscussionOur findings suggest that TNFRSF17 could serve as a potential therapeutic target for LN. Moreover, IBI379 is presented as a promising treatment option for LN.

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“…IL-17A may cause human airway epithelial cells to be insensitivity to corticosteroids. In human fibroblast MRC5 cells, IL-17 increased type I collagen production, upregulated glucocorticoid receptor β (GR-β) expression, and impaired the inhibitory effect of glucocorticoids on type I collagen and extracellular matrix production in pulmonary fibrosis (Lo et al 2022). A recent study showed that IL-17A does inhibited typical corticosteroid genes, such as HSD11B2 and FKBP5 (Rahmawati et al 2022).…”

Section: Balf Cytokines Changes In Ici-pneumonitis Patientsmentioning

confidence: 99%

Characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for immune checkpoint inhibitor-related pneumonitis

Wang

Zhang

et al. 2023

J Cancer Res Clin Oncol

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As immune checkpoint inhibitors (ICIs) are widely used, a series of immune-related adverse events (irAEs) have been reported, including immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis). The incidence of ICI-pneumonitis is higher in reality than in clinical trials. The diagnosis is challenging, mainly based on clinical and imaging features, and requires the exclusion of other causes. The data on the biological mechanisms of ICI-pneumonitis are scarce, resulting in little knowledge of the best treatment for ICI-pneumonitis. Bronchoalveolar lavage (BAL) may be helpful to identify the biological differences or find predictive biomarkers, and may in turn help to develop phenotype-specific targeted drugs to treat ICI-pneumonitis. Herein, we outline the characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for ICI-pneumonitis. Through careful sorting and literature review, we find crosstalk between pathogenic Th17/Th1 cells (i.e., Th17.1) and pro-inflammatory monocytes, and activation of Th17(/Th1)/IL-17A (/IFN-γ) pathways may play a key role in the pathogenesis of ICI-pneumonitis. Disruption of the interaction between pathogenic Th17/Th1 cells and pro-inflammatory monocytes (such as, anti-IL-23) may be a potential treatment for ICI-pneumonitis. We first describe the possible pathophysiological mechanisms of ICI-pneumonitis, hoping to contribute to the optimization of diagnosis and treatment, as well as provide readers with research inspiration.

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Increased Interleukin-17 and Glucocorticoid Receptor-β Expression in Interstitial Lung Diseases and Corticosteroid Insensitivity

Cited by 9 publications

References 49 publications

Th17 Cells, Glucocorticoid Resistance, and Depression

Th17 Cells, Glucocorticoid Resistance, and Depression

Uncovering lupus nephritis-specific genes and the potential of TNFRSF17-targeted immunotherapy: a high-throughput sequencing study

Characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for immune checkpoint inhibitor-related pneumonitis

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