scholarly journals Interleukin-33-Dependent Accumulation of Regulatory T Cells Mediates Pulmonary Epithelial Regeneration During Acute Respiratory Distress Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Tan ◽  
Bohan Zhang ◽  
Xinpei Liu ◽  
Chaoji Zhang ◽  
Jianzhou Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Respiratory Distress Syndrome ◽  
Regulatory T Cells ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Treg Cell ◽  
Distress Syndrome ◽  
Treg Cells ◽  
Epithelial Regeneration ◽  
Tgf Β1

Acute respiratory distress syndrome (ARDS) triggered mostly by infection, is a syndrome that involves respiratory failure. ARDS induces strong local infiltration of regulatory T cells (Treg cells) in the lungs, and Treg cells were recently highlighted as being related to the repair of various tissue. However, at present, there is still a lack of adequate evidence showing the impact of Treg cells on pulmonary regeneration during ARDS. Here, we verified that Treg cells are strongly induced in ARDS mice and Treg depletion results in impaired lung repair. Moreover, Treg cells show high expression of ST2, a cellular receptor for the tissue alarmin IL-33, which is strongly upregulated in the lung during ARDS. In addition, we demonstrated that IL-33 signaling is crucial for Treg cell accumulation, and ST2-blocked mice show a decrease in the Treg cell population. Critically, transfer of exogenous IL-33 into Treg depleted mice restored Treg cells and facilitated lung regeneration by promoting alveolar type II cell (AEC2) recovery in ARDS, with elevated neutrophils infiltration and upregulated TGF-β1 release. These results emphasized the importance of IL-33 in accelerating the expansion of pulmonary Treg cells and promoting their activity to mediate pulmonary epithelial regeneration during ARDS in a TGF-β1-dependent manner.

scholarly journals Regulatory T Cells for Treating Patients With COVID-19 and Acute Respiratory Distress Syndrome: Two Case Reports

2020 ◽  
Vol 173 (10) ◽  
pp. 852-853 ◽  
Author(s):  
Douglas E. Gladstone ◽  
Bo Soo Kim ◽  
Kathy Mooney ◽  
Andrew H. Karaba ◽  
Franco R. D'Alessio
Keyword(s):  
T Cells ◽  
Acute Respiratory Distress Syndrome ◽  
Regulatory T Cells ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Case Reports

scholarly journals The Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome by Downregulating miRNA that Target Inflammatory Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Muthanna Sultan ◽  
Hasan Alghetaa ◽  
Amirah Mohammed ◽  
Osama A. Abdulla ◽  
Paul J. Wisniewski ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Viral Infections ◽  
Suppressor Cells ◽  
Inflammatory Cell Infiltrate ◽  
Down Regulation ◽  
Inflammatory Phenotypes

Acute respiratory distress syndrome (ARDS) is defined as a type of respiratory failure that is caused by a variety of insults such as pneumonia, sepsis, trauma and certain viral infections. In this study, we investigated the effect of an endocannabinoid, anandamide (AEA), on ARDS induced in the mouse by Staphylococcus Enterotoxin B (SEB). Administration of a single intranasal dose of SEB in mice and treated with exogenous AEA at a dose of 40 mg/kg body weight led to the amelioration of ARDS in mice. Clinically, plethysmography results indicated that there was an improvement in lung function after AEA treatment accompanied by a decrease of inflammatory cell infiltrate. There was also a significant decrease in pro-inflammatory cytokines IL-2, TNF-α, and IFN-γ, and immune cells including CD4+ T cells, CD8+ T cells, Vβ8+ T cells, and NK+ T cells in the lungs. Concurrently, an increase in anti-inflammatory phenotypes such as CD11b + Gr1+ Myeloid-derived Suppressor Cells (MDSCs), CD4 + FOXP3 + Tregs, and CD4+IL10 + cells was observed in the lungs. Microarray data showed that AEA treatment in ARDS mice significantly altered numerous miRNA including downregulation of miRNA-23a-3p, which caused an upregulation of arginase (ARG1), which encodes for arginase, a marker for MDSCs, as well as TGF-β2, which induces Tregs. AEA also caused down-regulation of miRNA-34a-5p which led to induction of FoxP3, a master regulator of Tregs. Transfection of T cells using miRNA-23a-3p or miRNA-34a-5p mimics and inhibitors confirmed that these miRNAs targeted ARG1, TGFβ2 and FoxP3. In conclusion, the data obtained from this study suggests that endocannabinoids such as AEA can attenuate ARDS induced by SEB by suppressing inflammation through down-regulation of key miRNA that regulate immunosuppressive pathways involving the induction of MDSCs and Tregs.

scholarly journals Functional alteration of innate T cells in critically ill Covid-19 patients

2020 ◽  
Author(s):  
Youenn Jouan ◽  
Antoine Guillon ◽  
Loïc Gonzalez ◽  
Yonatan Perez ◽  
Stephan Ehrmann ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Distress Syndrome ◽  
Potential Contribution ◽  
Innate T Cells ◽  
Functional Alteration

AbstractCovid-19 can induce lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors in Covid-19-driven ARDS are poorly understood. Here, we dynamically analyzed the biology of innate T cells, a heterogeneous class (MAIT, γδT and iNKT cells) of T lymphocytes, presenting potent anti-infective and regulatory functions. Patients presented a compartmentalized lung inflammation paralleled with a limited systemic inflammation. Circulating innate T cells of critically ill Covid-19 patients presented a profound and persistent phenotypic and functional alteration. Highly activated innate T cells were detected in airways of patients suggesting a recruitment to the inflamed site and a potential contribution in the regulation of the local inflammation. Finally, the expression of the CD69 activation marker on blood iNKT and MAIT cells at inclusion was predictive of disease severity. Thus, patients present an altered innate T cell biology that may account for the dysregulated immune response observed in Covid-19-related acute respiratory distress syndrome.

Synergistic Inhibition of β2-adrenergic Receptor–mediated Alveolar Epithelial Fluid Transport by Interleukin-8 and Transforming Growth Factor-β

2015 ◽  
Vol 122 (5) ◽  
pp. 1084-1092 ◽  
Author(s):  
Brant M. Wagener ◽  
Jérémie Roux ◽  
Michel Carles ◽  
Jean-Francois Pittet
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Fluid Transport ◽  
Distress Syndrome ◽  
Transforming Growth Factor ◽  
Adenosine Monophosphate ◽  
Synergistic Inhibition ◽  
Alveolar Epithelial ◽  
Tgf Β1

Abstract Background: Patients with acute respiratory distress syndrome who retain maximal alveolar fluid clearance (AFC) have better clinical outcomes. The release of endogenous catecholamines associated with shock or the administration of β2-adrenergic receptor (β2AR) agonists enhances AFC via a 3′-5′-cyclic adenosine monophosphate–dependent mechanism. The authors have previously reported that transforming growth factor-β1 (TGF-β1) and interleukin-8 (IL-8), two major mediators of alveolar inflammation associated with the early phase of acute respiratory distress syndrome, inhibit AFC upregulation by β2AR agonists via a phosphoinositol-3-kinase (PI3K)–dependent mechanism. However, whether TGF-β1 and IL-8 cause an additive or synergistic inhibition of AFC is unclear. Thus, the central hypothesis of the study was to determine whether they synergistically inhibit the β2AR-stimulated AFC by activating two different isoforms of PI3K. Methods: The effects of TGF-β1 or IL-8 on β2AR agonist–stimulated net alveolar fluid transport were studied using short-circuit current studies. Molecular pathways of inhibition were confirmed by pharmacologic inhibitors and Western blotting of p-Akt, G-protein–coupled receptor kinase 2, protein kinase C-ζ, and phospho-β2AR. Finally, our observations were confirmed by an in vivo model of AFC. Results: Combined exposure to TGF-β1 and IL-8/cytokine-induced neutrophil chemoattractant-1 caused synergistic inhibition of β2AR agonist–stimulated vectorial Cl− across alveolar epithelial type II cells (n = 12 in each group). This effect was explained by activation of different isoforms of PI3K by TGF-β1 and IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each group). Furthermore, the inhibitory effect of TGF-β1 on 3′-5′-cyclic adenosine monophosphate–stimulated alveolar epithelial fluid transport required the presence of IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each group). Inhibition of cytokine-induced neutrophil chemoattractant-1 prevented TGF-β1–mediated heterologous β2AR downregulation and restored physiologic β2AR agonist–stimulated AFC in rats (n = 6 in each group). Conclusions: TGF-β1 and IL-8 have a synergistic inhibitory effect on β2AR-mediated stimulation of pulmonary edema removal by the alveolar epithelium. This result may, in part, explain why a large proportion of the patients with acute respiratory distress syndrome have impaired AFC.

scholarly journals Phenotype of SARS-CoV-2-specific T-cells in COVID-19 patients with acute respiratory distress syndrome

2020 ◽  
Author(s):  
Daniela Weiskopf ◽  
Katharina S. Schmitz ◽  
Matthijs P. Raadsen ◽  
Alba Grifoni ◽  
Nisreen M.A. Okba ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Respiratory Distress Syndrome ◽  
Immune Responses ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Protein S ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Th1 Cytokines

AbstractCOVID-19 is associated with lymphopenia and ‘cytokine storm’, but no information is available on specific cellular immune responses to SARS-CoV-2. Here, we characterized SARS-CoV-2-specific CD4+ and CD8+ T-cells in patients with acute respiratory distress syndrome. The spike protein (S) proved a potent T-cell antigen and specific T-cells predominantly produced Th1 cytokines. These novel data are important in vaccine design and will facilitate evaluation of vaccine candidate immunogenicity.

Sign in / Sign up

Export Citation Format

Share Document