Mucosal Associated Invariant T Cells Were Activated and Polarized Toward Th17 in Chronic Obstructive Pulmonary Disease

Qiu, Wenjia; Kang, Ning; Wu, Yanxu; Cai, Yongjun; Xiao, Li; Ge, Heng; Zhu, Huili

doi:10.3389/fimmu.2021.640455

Cited by 6 publications

(7 citation statements)

References 59 publications

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“…Majority of circulating MAIT cells secrete IFN-g and TNF-a after stimulation with PMA and ionomycin, while only a minority of them produce IL-17 (14). Functional impairment of blood MAIT cells with decreased IFN-g and increased IL-17 has been reported in patients with COPD and COVID-19 (26,27). In our study, the proportion of IFN-g+ cells was lower in blood MAIT cells of CAP patients compared to healthy controls.…”

Section: Discussionsupporting

confidence: 46%

Activation and Functional Alteration of Mucosal-Associated Invariant T Cells in Adult Patients With Community-Acquired Pneumonia

Ouyang

Shen

et al. 2021

Front. Immunol.

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Community-acquired pneumonia (CAP) remains the significant infectious cause of morbidity and mortality worldwide. Although mucosal-associated invariant T cells (MAIT) play roles in the pathogenesis of children CAP and ICU-associated pneumonia, their roles in adult CAP are largely unexplored. In this study, we investigated the frequency, phenotype, and function of MAIT cells in peripheral blood and bronchoalveolar lavage fluid (BALF) of adult CAP patients. Our data indicate that MAIT-cell frequency is profoundly lower in the peripheral blood of CAP patients compared to that in healthy individuals. Furthermore, the circulatory MAIT cells express higher levels of CD69 and PD-1 compared to those in healthy individuals. In BALF of CAP patients, MAIT-cell frequency is higher and MAIT cells express higher levels of CD69 and PD-1 compared to their matched blood counterparts. Levels of IL-17A and IFN-γ are increased in BALF of CAP patients compared to those in BALF of patients with pulmonary small nodules. The IL-17A/IFN-γ ratio is significantly positively correlated with MAIT frequency in BALF of CAP patients, suggesting a pathogenic role of MAIT-17 cells in CAP. Of note, blood MAIT-cell frequency in CAP patients is strongly negatively correlated with high-sensitivity C-reactive protein (hsCRP) and neutrophil count percentage in blood. The ability of circulating MAIT cells in CAP patients to produce IFN-γ is significantly impaired compared to those in healthy individuals. In summary, our findings suggest the possible involvement of MAIT cells in the immunopathogenesis of adult CAP.

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Section: Discussionsupporting

confidence: 46%

Activation and Functional Alteration of Mucosal-Associated Invariant T Cells in Adult Patients With Community-Acquired Pneumonia

Ouyang

Shen

et al. 2021

Front. Immunol.

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“…A further study has reported MAIT cell depletion in blood with enrichment in lung parenchyma and accumulation around alveolar epithelial cells in less clinically severe disease, however a limitation of these data is the lack of reporting on ICS use in lung tissue donors (152). There is a higher frequency of IL-17 + lung MAIT cells in COPD compared to health, and blood MAIT cells generate IL-17 (over IFN-g) following PMA-ionomycin stimulation in vitro with diminishing magnitude of response seen with worsening airflow obstruction (152). Lower MAIT cell frequencies are associated with elevated serum C-reactive protein (CRP) levels ( 153) and increased frequency of exacerbations requiring hospitalization (154).…”

Section: The Lower Airwaymentioning

confidence: 99%

“…MAIT cells are depleted in blood and endobronchial biopsies of corticosteroid treated (but not ICS naïve) COPD patients (129). A further study has reported MAIT cell depletion in blood with enrichment in lung parenchyma and accumulation around alveolar epithelial cells in less clinically severe disease, however a limitation of these data is the lack of reporting on ICS use in lung tissue donors (152). There is a higher frequency of IL-17 + lung MAIT cells in COPD compared to health, and blood MAIT cells generate IL-17 (over IFN-g) following PMA-ionomycin stimulation in vitro with diminishing magnitude of response seen with worsening airflow obstruction (152).…”

Section: The Lower Airwaymentioning

confidence: 99%

MAIT cells and the microbiome

Jabeen

Hinks

2023

Front. Immunol.

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Mucosal associated invariant T (MAIT) cells are innate-like T lymphocytes, strikingly enriched at mucosal surfaces and characterized by a semi-invariant αβ T cell receptor (TCR) recognizing microbial derived intermediates of riboflavin synthesis presented by the MHC-Ib molecule MR1. At barrier sites MAIT cells occupy a prime position for interaction with commensal microorganisms, comprising the microbiota. The microbiota is a rich source of riboflavin derived antigens required in early life to promote intra-thymic MAIT cell development and sustain a life-long population of tissue resident cells. A symbiotic relationship is thought to be maintained in health whereby microbes promote maturation and homeostasis, and in turn MAIT cells can engage a TCR-dependent “tissue repair” program in the presence of commensal organisms conducive to sustaining barrier function and integrity of the microbial community. MAIT cell activation can be induced in a MR1-TCR dependent manner or through MR1-TCR independent mechanisms via pro-inflammatory cytokines interleukin (IL)-12/-15/-18 and type I interferon. MAIT cells provide immunity against bacterial, fungal and viral pathogens. However, MAIT cells may have deleterious effects through insufficient or exacerbated effector activity and have been implicated in autoimmune, inflammatory and allergic conditions in which microbial dysbiosis is a shared feature. In this review we summarize the current knowledge on the role of the microbiota in the development and maintenance of circulating and tissue resident MAIT cells. We also explore how microbial dysbiosis, alongside changes in intestinal permeability and imbalance between pro- and anti-inflammatory components of the immune response are together involved in the potential pathogenicity of MAIT cells. Whilst there have been significant improvements in our understanding of how the microbiota shapes MAIT cell function, human data are relatively lacking, and it remains unknown if MAIT cells can conversely influence the composition of the microbiota. We speculate whether, in a human population, differences in microbiomes might account for the heterogeneity observed in MAIT cell frequency across mucosal sites or between individuals, and response to therapies targeting T cells. Moreover, we speculate whether manipulation of the microbiota, or harnessing MAIT cell ligands within the gut or disease-specific sites could offer novel therapeutic strategies.

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“…Although MR1 expression has been confirmed in all cell types studied to-date 38 , nearly all analyses of MR1 expression and regulation have focused on the surface expression of MR1 protein. There are a limited number of studies examining MR1 gene expression in bulk cells from ( the lung parenchyma or peripheral blood of COPD donors 24,25 , however we are unaware of any analysis of the impact of COPD or CS exposure on MR1 expression in primary BEC. Therefore, we looked at MR1 gene expression in BEC from COPD and smoker lungs compared to healthy controls and sought to determine if exposure to CSE had any impact on MR1 mRNA expression in BEC from all donors.…”

Section: Acute Cs Exposure Does Not Impact Transcriptional Regulation...mentioning

confidence: 99%

“…Mucosal-associated invariant T (MAIT) cells are an innate-like subset of T lymphocytes that make up a relatively large proportion of the total CD8 + T cell population in the blood and lungs in healthy individuals 21 . Interestingly, despite the overall increase in CD8 + T cells in COPD, the frequency of both peripheral blood and lung-resident MAIT cells in individuals with COPD is decreased [22][23][24][25] . This observation is different from many other infectious and inflammatory lung conditions, and the mechanisms underlying MAIT cell loss in COPD lungs are not yet defined.…”

Section: Introductionmentioning

confidence: 97%

Chronic obstructive pulmonary disease and cigarette smoke exposure lead to dysregulated MAIT cell activation by bronchial epithelial cells

Huber

Larson

Lust

et al. 2022

Preprint

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Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation, increased infiltration by CD8+ T lymphocytes, and infection-driven exacerbations. COPD is most commonly caused by cigarette smoke (CS), however the mechanisms driving development of COPD in some smokers but not others are incompletely understood. Lung-resident mucosal-associated invariant T (MAIT) cells play a role in both microbial infections and inflammatory diseases. MAIT cell frequency is reduced in the peripheral blood of individuals with COPD, however the role of MAIT cells in COPD pathology is unknown. Here, we examined MAIT cell activation in response to CS-exposed primary human bronchial epithelial cells (BEC) from healthy, COPD, or smoker donors. We observed significantly higher MAIT cell responses to COPD BEC than healthy BEC. However, COPD BEC stimulated a smaller fold-increase in MAIT cell response despite increased microbial infection. For all donor groups, CS-exposed BEC elicited reduced MAIT cell responses; conversely, CS exposure increased ligand-mediated MR1 surface translocation in healthy and COPD BEC. Our data demonstrate MAIT cell activation is dysregulated in the context of CS and COPD. MAIT cells could contribute to CS- and COPD-associated inflammation through both inappropriate activation and reduced early recognition of bacterial infection, contributing to microbial persistence and COPD exacerbations.

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Mucosal Associated Invariant T Cells Were Activated and Polarized Toward Th17 in Chronic Obstructive Pulmonary Disease

Cited by 6 publications

References 59 publications

Activation and Functional Alteration of Mucosal-Associated Invariant T Cells in Adult Patients With Community-Acquired Pneumonia

Activation and Functional Alteration of Mucosal-Associated Invariant T Cells in Adult Patients With Community-Acquired Pneumonia

MAIT cells and the microbiome

Chronic obstructive pulmonary disease and cigarette smoke exposure lead to dysregulated MAIT cell activation by bronchial epithelial cells

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