Respiratory infections regulated blood cells IFN‐β‐PD‐L1 pathway in pediatric asthma

Kölle, Julia; Haag, Patricia; Vuorinen, Tytti; Krause, Alexander; Rauh, Manfred; Zimmermann, Theodor; Papadopoulos, Nikolaos G.; Finotto, Susetta

doi:10.1002/iid3.307

Cited by 4 publications

(5 citation statements)

References 18 publications

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“…In the same cohort was found that the released levels of IFN-b from PBMCs were associated with an induction of PD-L1, however only in the control group (112). In the asthma group, the asthmatic patients with higher IFN-ß level have less PD-L1 expression in total blood cells and better lung function (112). This finding suggests that IFN-ß suppresses PD-L1 expression in asthma, and the improvement of IFN type I expression in PBMCs in pediatric asthma may ameliorate asthma exacerbation.…”

Section: Pd-l1mentioning

confidence: 84%

“…In a human cohort study, it was recently described that preschoolers suffering from rhinovirus-induces asthma and with reduced forced expiratory volume in 1 second (FEV1) and high serum levels of C-reactive protein (CRP) show increased level of PD-L1 mRNA in total blood cells. In the same cohort was found that the released levels of IFN-b from PBMCs were associated with an induction of PD-L1, however only in the control group (112). In the asthma group, the asthmatic patients with higher IFN-ß level have less PD-L1 expression in total blood cells and better lung function (112).…”

Section: Pd-l1mentioning

confidence: 94%

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Mechanism of Rhinovirus Immunity and Asthma

et al. 2021

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The majority of asthma exacerbations in children are caused by Rhinovirus (RV), a positive sense single stranded RNA virus of the Picornavirus family. The host has developed virus defense mechanisms that are mediated by the upregulation of interferon-activated signaling. However, the virus evades the immune system by inducing immunosuppressive cytokines and surface molecules like programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on immunocompetent cells. Initially, RV infects epithelial cells, which constitute a physiologic mucosal barrier. Upon virus entrance, the host cell immediately recognizes viral components like dsRNA, ssRNA, viral glycoproteins or CpG-DNA by host pattern recognition receptors (PRRs). Activation of toll like receptors (TLR) 3, 7 and 8 within the endosome and through MDA-5 and RIG-I in the cytosol leads to the production of interferon (IFN) type I and other antiviral agents. Every cell type expresses IFNAR1/IFNAR2 receptors thus allowing a generalized antiviral activity of IFN type I resulting in the inhibition of viral replication in infected cells and preventing viral spread to non-infected cells. Among immune evasion mechanisms of the virus, there is downregulation of IFN type I and its receptor as well as induction of the immunosuppressive cytokine TGF-β. TGF-β promotes viral replication and is associated with induction of the immunosuppression signature markers LAP3, IDO and PD-L1. This article reviews the recent advances on the regulation of interferon type I expression in association with RV infection in asthmatics and the immunosuppression induced by the virus.

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Section: Pd-l1mentioning

confidence: 84%

Section: Pd-l1mentioning

confidence: 94%

Mechanism of Rhinovirus Immunity and Asthma

et al. 2021

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“…A short cohort study showed that in the control group, the IFN released by PBMC was related to the production of PD-L1. Yet, the study also showed that higher IFN-β levels were associated with the lower level of PD-L1 and better lung function ( 87 ). To summarize, PD-L1 might be a pro-inflammatory cytokine in RV-related asthmatics.…”

Section: Cytokines Produced In Rv-induced Immunoreactionsmentioning

confidence: 99%

Immunotherapeutic implications on targeting the cytokines produced in rhinovirus-induced immunoreactions

Sang,

Gong,

Huang

et al. 2024

Front. Allergy

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Rhinovirus is a widespread virus associated with several respiratory diseases, especially asthma exacerbation. Currently, there are no accurate therapies for rhinovirus. Encouragingly, it is found that during rhinovirus-induced immunoreactions the levels of certain cytokines in patients' serum will alter. These cytokines may have pivotal pro-inflammatory or anti-inflammatory effects via their specific mechanisms. Thus far, studies have shown that inhibitions of cytokines such as IL-1, IL-4, IL-5, IL-6, IL-13, IL-18, IL-25, and IL-33 may attenuate rhinovirus-induced immunoreactions, thereby relieving rhinovirus infection. Furthermore, such therapeutics for rhinovirus infection can be applied to viruses of other species, with certain practicability.

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“…The human tissue explant model of viral infection maintains tissue-architecture during the infection process, including the presence of multiple inflammatory cell types, allowing the effect of asthma and viral infection to be compared in multiple resident cell types simultaneously. This model has been demonstrated to reflect human in-vivo viral tropism, influenza virus T cell epitope presentation, and inflammatory mediator release patterns more effectively than in-vitro cell systems, and we have previously demonstrated using lung parenchyma explants that PD-L1 expression patterns post-influenza infection are modulated in chronic obstructive pulmonary disease (5,9) Studies by others have suggested abnormal expression of the PD-1 pathway in atopic individuals and allergic asthma (10,11) but have not established whether anti-PD-1 therapy could be useful or detrimental in the treatment of allergic asthmatics in the context of acute viral exposure.…”

Section: Introductionmentioning

confidence: 99%

“…Studies by others have suggested abnormal expression of the PD-1 pathway in atopic individuals and allergic asthma ( 10 , 11 ) but have not established whether anti-PD-1 therapy could be useful or detrimental in the treatment of allergic asthmatics in the context of acute viral exposure.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory regulator blockade in a viral exacerbation model of severe asthma

et al. 2022

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Asthmatics are more susceptible to viral infections than healthy individuals and are known to have impaired innate anti-viral defences. Influenza A virus causes significant morbidity and mortality in this population. Immuno-modulatory regulators (IMRs) such as PD-1 are activated on T cells following viral infection as part of normal T cell activation responses, and then subside, but remain elevated in cases of chronic exposure to virus, indicative of T cell exhaustion rather than activation. There is evidence that checkpoint inhibition can enhance anti-viral responses during acute exposure to virus through enhancement of CD8+T cell function. Although elevated PD-1 expression has been described in pulmonary tissues in other chronic lung diseases, the role of IMRs in asthma has been relatively unexplored as the basis for immune dysfunction. We first assessed IMR expression in the peripheral circulation and then quantified changes in IMR expression in lung tissue in response to ex-vivo influenza infection. We found that the PD-1 family members are not significantly altered in the peripheral circulation in individuals with severe asthma but are elevated in pulmonary tissues following ex-vivo influenza infection. We then applied PD-1 Mab inhibitor treatment to bronchial biopsy tissues infected with influenza virus and found that PD-1 inhibition was ineffective in asthmatics, but actually increased infection rates in healthy controls. This study, therefore, suggests that PD-1 therapy would not produce harmful side-effects when applied in people with severe asthma, but could have important, as yet undescribed, negative effects on anti-viral responses in healthy individuals that warrant further investigation.

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Respiratory infections regulated blood cells IFN‐β‐PD‐L1 pathway in pediatric asthma

Cited by 4 publications

References 18 publications

Mechanism of Rhinovirus Immunity and Asthma

Mechanism of Rhinovirus Immunity and Asthma

Immunotherapeutic implications on targeting the cytokines produced in rhinovirus-induced immunoreactions

Immunomodulatory regulator blockade in a viral exacerbation model of severe asthma

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