Role of Th17 cell in tissue inflammation and organ-specific autoimmunity

Dalal, Rajdeep; Sadhu, Srikanth; Awasthi, Amit

doi:10.1016/b978-0-12-822564-6.00005-7

Cited by 3 publications

(4 citation statements)

References 161 publications

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“…For the differentiation and activation of functional T cells, the antigen-presenting cells (APCs) must provide three signals to the T cells. One is via direct TCR–MHC interaction, the second is through cognate interaction of adhesion molecules, and the third is by cytokine signaling [ 11 ]. Therefore, cytokines play a critical role in shaping the T cell response during exposure to a foreign antigen.…”

Section: Discussionmentioning

confidence: 99%

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Proinflammatory Innate Cytokines and Distinct Metabolomic Signatures Shape the T Cell Response in Active COVID-19

et al. 2022

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The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell responses during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0–3, 7–9, and 14–16 days post-COVID-19 positivity) from young, mildly symptomatic, active COVID-19 patients infected during the first wave in mid-2020. We observed that anti-RBD IgG and viral neutralization are significantly reduced against the delta variant, compared to the ancestral strain. In contrast, compared to the ancestral strain, T cell responses remain preserved against the delta and omicron variants. We determined innate immune responses during the early stage of active infection, in response to TLR 3/7/8-mediated activation in PBMCs and serum metabolomic profiling. Correlation analysis indicated PBMCs-derived proinflammatory cytokines, IL-18, IL-1β, and IL-23, and the abundance of plasma metabolites involved in arginine biosynthesis were predictive of a robust SARS-CoV-2-specific Th1 response at a later stage (two weeks after PCR positivity). These observations may contribute to designing effective vaccines and adjuvants that promote innate immune responses and metabolites to induce a long-lasting anti-SARS-CoV-2-specific T cell response.

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Section: Discussionmentioning

confidence: 99%

“…Antigen-presenting cells (APCs) provide secondary signals in the form of cytokines that are critical in modulating T cell activation and differentiation [ 11 ]. However, the phenotype of cytokines secreted by innate immune cells in generating a comprehensive T cell response is not clearly understood in COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory Innate Cytokines and Distinct Metabolomic Signatures Shape the T Cell Response in Active COVID-19

et al. 2022

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“…For the differentiation and activation of functional T cells, the antigen-presenting cells (APCs) must provide three signals to the T cells. One is via direct TCR-MHC interaction, the second is through cognate interaction of adhesion molecules, and the third is by cytokine signaling ( 11 ). Therefore, the APCs play a critical role in shaping the T cell response during exposure to a foreign antigen.…”

Section: Resultsmentioning

confidence: 99%

“…Antigen-presenting cells (APCs) provide secondary signals in the form of cytokines that are critical in modulating the T cell activation and differentiation ( 11 ). However, the phenotype of cytokines secreted by innate immune cells in generating a comprehensive T cell response is not clearly understood in COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory innate cytokines and metabolomic signatures shape the T cell response in active COVID-19

Binayke

Zaheer

Dandotiya

et al. 2022

Preprint

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The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell response during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0-4, 7-9, and 14-16 days post-COVID-19 positivity) from young mildly symptomatic active COVID-19 patients who got infected with ancestral virus. We observed the induction of anti-RBD and SARS-CoV-2 neutralizing antibodies together with antigen-specific T cell responses as early as 0-4 days post-infection. T cell responses were largely preserved against the delta and omicron variants as compared to the ancestral strain. We determined innate immune responses at an early (days 0-4 post-COVID-19 positivity) time point of active infection in response to TLR 3/7/8 mediated activation. Interestingly, the innate immune response exhibited by the elevated levels of IL-6, IL-1β, and IL-23 correlated with a robust SARS-CoV-2-specific Th1 response at the later time point (14-16 days post covid positivity). To further understand the association of metabolic pathways induced upon active COVID-19 infection with innate and T cell response, metabolomic profiling was performed. As compared to healthy individuals, COVID-19 patients displayed a distinct metabolic signature with an enrichment of pyroglutamate, itaconate, and azelaic acid, which correlated with the SARS-CoV-2-induced innate and T cells response. Our observations reveal mechanisms and potential interventional approaches that may assist in COVID-19 therapeutics and vaccine adjuvant strategies.

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IL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation

Sadhu,

Dalal,

Dandotiya

et al. 2023

Nat Commun

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SARS-CoV-2 infection is known for causing broncho-alveolar inflammation. Interleukin 9 (IL-9) induces airway inflammation and bronchial hyper responsiveness in respiratory viral illnesses and allergic inflammation, however, IL-9 has not been assigned a pathologic role in COVID-19. Here we show, in a K18-hACE2 transgenic (ACE2.Tg) mouse model, that IL-9 contributes to and exacerbates viral spread and airway inflammation caused by SARS-CoV-2 infection. ACE2.Tg mice with CD4+ T cell-specific deficiency of the transcription factor Forkhead Box Protein O1 (Foxo1) produce significantly less IL-9 upon SARS-CoV-2 infection than the wild type controls and they are resistant to the severe inflammatory disease that characterises the control mice. Exogenous IL-9 increases airway inflammation in Foxo1-deficient mice, while IL-9 blockade reduces and suppresses airway inflammation in SARS-CoV-2 infection, providing further evidence for a Foxo1-Il-9 mediated Th cell-specific pathway playing a role in COVID-19. Collectively, our study provides mechanistic insight into an important inflammatory pathway in SARS-CoV-2 infection, and thus represents proof of principle for the development of host-directed therapeutics to mitigate disease severity.

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Role of Th17 cell in tissue inflammation and organ-specific autoimmunity

Cited by 3 publications

References 161 publications

Proinflammatory Innate Cytokines and Distinct Metabolomic Signatures Shape the T Cell Response in Active COVID-19

Proinflammatory Innate Cytokines and Distinct Metabolomic Signatures Shape the T Cell Response in Active COVID-19

Proinflammatory innate cytokines and metabolomic signatures shape the T cell response in active COVID-19

IL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation

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