CD1d-Independent Activation of Invariant Natural Killer T Cells by Staphylococcal Enterotoxin B through Major Histocompatibility Complex Class II/T Cell Receptor Interaction Results in Acute Lung Injury

Rieder, Sadiye Amcaoglu; Nagarkatti, Mitzi; Nagarkatti, Mitzi

doi:10.1128/iai.00177-11

Cited by 34 publications

(39 citation statements)

References 36 publications

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“…Activation of iNKT cells by CD1d glycolipid presentation to TCRs has been shown to induce cytokines such as IFN-g and IL-4 (40). However, antigenindependent mechanisms have also been described that rapidly facilitate iNKT cell activation (41)(42)(43)(44)(45). In support of this, Nowak-Machen and colleagues showed that pulmonary iNKT cells secreted significant levels of IFN-g and IL-17 after exposure to hyperoxia (46).…”

Section: Original Articlementioning

confidence: 56%

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A_2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

Sharma

LaPar

Stone

et al. 2016

Am J Respir Crit Care Med

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Rationale: Ischemia-reperfusion (IR) injury after lung transplantation, which affects both short-and long-term allograft survival, involves activation of NADPH oxidase 2 (NOX2) and activation of invariant natural killer T (iNKT) cells to produce IL-17. Adenosine A 2A receptor (A 2A R) agonists are known to potently attenuate lung IR injury and IL-17 production. However, mechanisms for iNKT cell activation after IR and A 2A R agonist-mediated protection remain unclear.Objectives: We tested the hypothesis that NOX2 mediates IL-17 production by iNKT cells after IR and that A 2A R agonism prevents IR injury by blocking NOX2 activation in iNKT cells.Methods: An in vivo murine hilar ligation model of IR injury was used, in which left lungs underwent 1 hour of ischemia and 2 hours of reperfusion.Measurements and Main Results: Adoptive transfer of iNKT cells from p47 phox2/2 or NOX2 2/2 mice to Ja18 2/2 (iNKT cell-deficient) mice significantly attenuated lung IR injury and IL-17 production. Treatment with an A 2A R agonist attenuated IR injury and IL-17 production in wild-type (WT) mice and in Ja18 2/2 mice reconstituted with WT, but not A 2A R 2/2, iNKT cells. Furthermore, the A 2A R agonist prevented IL-17 production by murine and human iNKT cells after acute hypoxia-reoxygenation by blocking p47 phox phosphorylation, a critical step for NOX2 activation.Conclusions: NOX2 plays a key role in inducing iNKT cell-mediated IL-17 production and subsequent lung injury after IR. A primary mechanism for A 2A R agonist-mediated protection entails inhibition of NOX2 in iNKT cells. Therefore, agonism of A 2A Rs on iNKT cells may be a novel therapeutic strategy to prevent primary graft dysfunction after lung transplantation.

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Section: Original Articlementioning

confidence: 56%

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A_2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

Sharma

LaPar

Stone

et al. 2016

Am J Respir Crit Care Med

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“…Previously, a single dose of SEB (50 g) by intranasal delivery was found to induce cellular infiltration, increase cytokine production, and cause histopathological lesions and edema in C57BL/6 mice (4, 21,22), mimicking the symptoms of acute inflammatory lung injury in humans (23). In this study, we first sought to investigate the inflammatory effect of SEB exposure in the lungs.…”

Section: Resultsmentioning

confidence: 99%

“…SEB dissolved in sterile phosphate-buffered saline (PBS) (2 mg/ml) was administered by the intranasal (i.n.) route in a volume of 25 l for a dose of 50 g per mouse, as described previously (4,21,22). Mice were euthanized 48 h after SEB exposure.…”

Section: Methodsmentioning

confidence: 99%

Staphylococcal Enterotoxin B-Induced MicroRNA-155 Targets SOCS1 To Promote Acute Inflammatory Lung Injury

Rao

Nagarkatti

2014

Infect Immun

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Staphylococcal enterotoxin B (SEB) causes food poisoning in humans. It is considered a biological weapon, and inhalation can trigger lung injury and sometimes respiratory failure. Being a superantigen, SEB initiates an exaggerated inflammatory response. While the role of microRNAs (miRNAs) in immune cell activation is getting increasing recognition, their role in the regulation of inflammatory disease induced by SEB has not been studied. In this investigation, we demonstrate that exposure to SEB by inhalation results in acute inflammatory lung injury accompanied by an altered miRNA expression profile in lung-infiltrating cells. Among the miRNAs that were significantly elevated, miR-155 was the most overexpressed. Interestingly, miR-155 ؊/؊ mice were protected from SEB-mediated inflammation and lung injury. Further studies revealed a functional link between SEB-induced miR-155 and proinflammatory cytokine gamma interferon (IFN-␥). Through the use of bioinformatics tools, suppressor of cytokine signaling 1 (SOCS1), a negative regulator of IFN-␥, was identified as a potential target of miR-155. While miR-155 ؊/؊ mice displayed increased expression of Socs1, the overexpression of miR-155 led to its suppression, thereby enhancing IFN-␥ levels. Additionally, the inhibition of miR-155 resulted in restored Socs1expression. Together, our data demonstrate an important role for miR-155 in promoting SEB-mediated inflammation in the lungs through Socs1 suppression and suggest that miR-155 may be an important target in preventing SEB-mediated inflammation and tissue injury.

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“…SEB binds to the nonpolymorphic regions of MHC II on antigen presenting cells and the specific V␤ regions of the T-cell receptor (TCR) such as murine V␤8, thereby activating a large population (up to 30%) of T cells that proliferate rapidly and trigger cytokine storm (17). Recent studies from our laboratory demonstrated that THC can attenuate SEB-mediated inflammation and toxicity to the lungs (18 -20).…”

mentioning

confidence: 99%

RNA-seq Analysis of δ9-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation

Yang

Bam

Nagarkatti

2016

Journal of Biological Chemistry

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Marijuana has drawn significant public attention and concern both for its medicinal and recreational use. ⌬9-Tetrahydrocannabinol (THC), which is the main bioactive component in marijuana, has also been shown to possess potent anti-inflammatory properties by virtue of its ability to activate cannabinoid receptor-2 (CB-2) expressed on immune cells. In this study, we used RNA-seq to quantify the transcriptomes and transcript variants that are differentially regulated by THC in super antigen-activated lymph node cells and CD4 ؉ T cells. We found that the expressions of many transcripts were altered by THC in both total lymph node cells and CD4 ؉ T cells. Furthermore, the abundance of many miRNA precursors and long non-coding RNAs was dramatically altered in THC-treated mice. For example, the expression of miR-17/92 cluster and miR-374b/421 cluster was down-regulated by THC. On the other hand miR146a, which has been shown to induce apoptosis, was up-regulated by THC. Long non-coding RNAs that are expressed from the opposite strand of CD27 and Appbp2 were induced by THC. In addition, THC treatment also caused alternative promoter usage and splicing. The functions of those altered transcripts were mainly related to immune response and cell proliferation.Marijuana (Cannabis sativa) is the most widely used drug of abuse in the United States. Nonetheless, it is worth noting that its medicinal value has been known for many centuries and is getting increasing recognition in recent times. Thus, ⌬9-tetrahydrocannabinol (THC), 2 the major psychoactive principle in marijuana, is used for medicinal purposes such as for pain relief as well as an anti-emetic and appetite stimulant during cancer chemotherapy and in HIV/AIDS patients (1). In addition, marijuana is widely known anecdotally for its use to relieve pain, and prevent seizures in patients with epilepsy. Because of the potential therapeutic value of marijuana in a variety of clinical disorders, 23 states and the District of Columbia currently have laws legalizing marijuana for medicinal use. Four states and the District of Columbia have also legalized marijuana for recreational use. Clearly, legalization of marijuana for medicinal or recreational purposes raises significant questions on its long term use/abuse and the impact on human health.THC has also been shown to modulate immune response primarily through activation of cannabinoid receptors (CB2) expressed primarily on cells of the immune system (2-4). In general, most studies have shown that THC has immunosuppressive properties mediated through multiple pathways (2, 5, 6). For example, it has been shown that THC suppresses Th1, whereas promoting Th2 cells (7). THC has also been shown to induce apoptosis in immune cells (8, 9), and induce myeloidderived suppressor cells and Tregs, which are known to inhibit T cell proliferation (10 -12). Moreover, induction of myeloidderived suppressor cell by THC is associated with altered microRNA expression (13). Our previous studies have shown that epigenetic modifications such as...

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CD1d-Independent Activation of Invariant Natural Killer T Cells by Staphylococcal Enterotoxin B through Major Histocompatibility Complex Class II/T Cell Receptor Interaction Results in Acute Lung Injury

Cited by 34 publications

References 36 publications

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A_2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A_2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

Staphylococcal Enterotoxin B-Induced MicroRNA-155 Targets SOCS1 To Promote Acute Inflammatory Lung Injury

RNA-seq Analysis of δ9-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation

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CD1d-Independent Activation of Invariant Natural Killer T Cells by Staphylococcal Enterotoxin B through Major Histocompatibility Complex Class II/T Cell Receptor Interaction Results in Acute Lung Injury

Cited by 34 publications

References 36 publications

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

Staphylococcal Enterotoxin B-Induced MicroRNA-155 Targets SOCS1 To Promote Acute Inflammatory Lung Injury

RNA-seq Analysis of δ9-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation

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Product

Resources

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NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A_2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A_2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury