Antiviral Responses of Tissue-resident CD49a<sup>+</sup> Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease

Cooper, Grace E.; Mayall, Jemma; Donovan, Chantal; Haw, Tatt Jhong; Budden, Kurtis F.; Blomme, Evy; Maes, Tania; Kong, Chia Wei; Horvat, Jay; Khakoo, Salim I.; Wilkinson, Tom; Hansbro, Philip M.; Staples, Karl J.

doi:10.1164/rccm.202205-0848oc

Cited by 7 publications

(5 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD103 binds E-cadherin on epithelial cells, thereby promoting cell accumulation in intestinal, cutaneous, bronchial, and genital epithelia [ 49 , 50 ]. CD49a and CD49b are collagen-binding integrins that primarily adhere to type IV and I collagen [ 51 – 53 ]. Other molecules, such as antigen-specific T cell receptors [ 54 , 55 ] and some chemokine receptors [ 56 – 58 ] (e.g., CXCR4 and CCR7), are also implicated in cell retention through recognition of cognate antigens or constitutively expressed chemotactic ligands by structural cells [ 57 ].…”

Section: Immune Cell Traffickingmentioning

confidence: 99%

Immune cell trafficking: a novel perspective on the gut-skin axis

Zhang,

Yao

2024

Inflamm Regener

View full text Add to dashboard Cite

Immune cell trafficking, an essential mechanism for maintaining immunological homeostasis and mounting effective responses to infections, operates under a stringent regulatory framework. Recent advances have shed light on the perturbation of cell migration patterns, highlighting how such disturbances can propagate inflammatory diseases from their origin to distal organs. This review collates and discusses current evidence that demonstrates atypical communication between the gut and skin, which are conventionally viewed as distinct immunological spheres, in the milieu of inflammation. We focus on the aberrant, reciprocal translocation of immune cells along the gut-skin axis as a pivotal factor linking intestinal and dermatological inflammatory conditions. Recognizing that the translation of these findings into clinical practices is nascent, we suggest that therapeutic strategies aimed at modulating the axis may offer substantial benefits in mitigating the widespread impact of inflammatory diseases.

show abstract

Section: Immune Cell Traffickingmentioning

confidence: 99%

Immune cell trafficking: a novel perspective on the gut-skin axis

Zhang,

Yao

2024

Inflamm Regener

View full text Add to dashboard Cite

show abstract

“…Mice were exposed to normal room air or CS from 12 3R4F cigarettes (University of Kentucky, Lexington, Kentucky, USA) twice per day, 5 days per week, for 8 or 12 weeks as previously described. [12][13][14][15][16][17][18][19][20] FMT was administered twice per week by transfer of soiled bedding or oral gavage of faecal supernatants from agematched air-exposed mice to CS-exposed mice and vice versa (online supplemental figure S1). Experimental controls were used as donors for the FMT to ensure the use of age-matched donors which had undergone microbiome normalisation, minimising variability and confounding factors (online supplemental figure S1).…”

Section: Mice Cs-exposure Microbiome Transfer and Diet Studiesmentioning

confidence: 99%

Faecal microbial transfer and complex carbohydrates mediate protection against COPD

Budden,

Shukla,

Bowerman

et al. 2024

Gut

Self Cite

View full text Add to dashboard Cite

ObjectiveChronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear.DesignUsing anin vivomouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation.ResultsFMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance ofMuribaculaceae, DesulfovibrionaceaeandLachnospiraceaefamily members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes.ConclusionThe gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

show abstract

“…In line with this, immune cells in COPD exhibit altered metabolic function, including glycolysis and fatty acid oxidation [ 54 , 55 , 56 , 57 , 58 ], which are important processes required for ATP production to fuel energy demanding immune functions [ 59 ]. Subsequently, immune cells in COPD exhibit impaired immune functions, including phagocytosis, altered viral response, and increased cytokine production [ 60 , 61 , 62 ], suggesting a self-perpetuating cycle in which ROS exposure both initiates and maintains mitochondrial and immune cell dysfunction in COPD, contributing to widespread destruction of the airways.…”

Section: Oxidative Stress In Copdmentioning

confidence: 99%

Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease

et al. 2023

Self Cite

View full text Add to dashboard Cite

Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging and cellular senescence. Evidence suggests that oxidative damage is not solely due to exogenous exposure to inhaled irritants, but also endogenous sources of oxidants in the form of reactive oxygen species (ROS). Mitochondria, the major producers of ROS, exhibit impaired structure and function in COPD, resulting in reduced oxidative capacity and excessive ROS production. Antioxidants have been shown to protect against ROS-induced oxidative damage in COPD, by reducing ROS levels, reducing inflammation, and protecting against the development of emphysema. However, currently available antioxidants are not routinely used in the management of COPD, suggesting the need for more effective antioxidant agents. In recent years, a number of mitochondria-targeted antioxidant (MTA) compounds have been developed that are capable of crossing the mitochondria lipid bilayer, offering a more targeted approach to reducing ROS at its source. In particular, MTAs have been shown to illicit greater protective effects compared to non-targeted, cellular antioxidants by further reducing apoptosis and offering greater protection against mtDNA damage, suggesting they are promising therapeutic agents for the treatment of COPD. Here, we review evidence for the therapeutic potential of MTAs as a treatment for chronic lung disease and discuss current challenges and future directions.

show abstract

Antiviral Responses of Tissue-resident CD49a⁺ Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease

Cited by 7 publications

References 48 publications

Immune cell trafficking: a novel perspective on the gut-skin axis

Immune cell trafficking: a novel perspective on the gut-skin axis

Faecal microbial transfer and complex carbohydrates mediate protection against COPD

Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease

Contact Info

Product

Resources

About

Antiviral Responses of Tissue-resident CD49a+ Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease

Cited by 7 publications

References 48 publications

Immune cell trafficking: a novel perspective on the gut-skin axis

Immune cell trafficking: a novel perspective on the gut-skin axis

Faecal microbial transfer and complex carbohydrates mediate protection against COPD

Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease

Contact Info

Product

Resources

About

Antiviral Responses of Tissue-resident CD49a⁺ Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease