Skewed Lung CCR4 to CCR6 CD4+ T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function

Adegunsoye, Ayodeji; Hrusch, Cara L.; Bonham, Catherine A.; Jaffery, Mohammad R.; Blaine, Kelly M.; Sullivan, Molly; Churpek, Matthew M.; Strek, Mary E.; Noth, Imre; Sperling, Anne I.

doi:10.3389/fimmu.2016.00516

Cited by 33 publications

(22 citation statements)

References 55 publications

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“…Pulmonary disorders with a robust immunologic response are frequently characterized by enlarged MLNs (31)(32)(33)(34)(35)(36)(37), which are a hallmark of ongoing immune response within the tissue. We have recently demonstrated that IPF lungs contain high numbers of immune cells, especially T cells, and that these T cells have distinct phenotypic markers when compared with lung T cells from patients without fibrotic lung disease (11). We found these same phenotypic differences in the MLNs, which suggests the trafficking of effector immune cells from the lungs to the MLNs (11).…”

Section: Discussionmentioning

confidence: 50%

“…Mediastinal lymph nodes (MLNs) are often enlarged on chest CT scans in patients with ILD, and they have been reported in up to 70% of patients with a usual interstitial pneumonia pattern (9,10). The biology underpinning MLN enlargement remains unclear, but trafficking of immune cells from the peripheral circulation through MLNs to the lungs has been suggested as contributory to pulmonary fibrosis (11). Recent data also suggest that the background lung microbiome may influence the expression of genes with known immunologic function, including IL-6 and IL-10, which have been linked to ILD outcomes (12,13).…”

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confidence: 99%

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Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation

Adegunsoye

Oldham

Bonham

et al. 2019

Am J Respir Crit Care Med

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Section: Discussionmentioning

confidence: 50%

mentioning

confidence: 99%

Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation

Adegunsoye

Oldham

Bonham

et al. 2019

Am J Respir Crit Care Med

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“…Fifty million lung leukocytes were thawed and centrifuged over Histopaque 1077 (Sigma, St Louis, Mo) gradient, as previously described. E4 Cells were then stained with antibodies for fluorescence-activated cell sorting of CD4 TRMs with the CD45 + CD206 − CD14 − CD3 + CD11b − CD4 + CD8 − CDRO + CD11a + phenotype. RNA was extracted from cells by using AllPrep DNA/RNA Mini Kits (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

A decade of research on the 17q12-21 asthma locus: Piecing together the puzzle

Stein

Thompson

Schoettler

et al. 2018

Journal of Allergy and Clinical Immunology

149

171

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Chromosome 17q12–21 remains the most highly replicated and significant asthma locus. Genotypes in the core region defined by the first genome-wide association study correlate with expression of 2 genes, ORM1-like 3 (ORMDL3) and gasdermin B (GSDMB), making these prime candidate asthma genes, although recent studies have implicated gasdermin A (GSDMA) distal to and post-GPI attachment to proteins 3 (PGAP3) proximal to the core region as independent loci. We review 10 years of studies on the 17q12–21 locus and suggest that genotype-specific risks for asthma at the proximal and distal loci are not specific to early-onset asthma and mediated by PGAP3, ORMDL3, and/or GSDMA expression. We propose that the weak and inconsistent associations of 17q single nucleotide polymorphisms with asthma in African Americans is due to the high frequency of some 17q alleles, the breakdown of linkage disequilibrium on African-derived chromosomes, and possibly different early-life asthma endotypes in these children. Finally, the inconsistent association between asthma and gene expression levels in blood or lung cells from older children and adults suggests that genotype effects may mediate asthma risk or protection during critical developmental windows and/or in response to relevant exposures in early life. Thus studies of young children and ethnically diverse populations are required to fully understand the relationship between genotype and asthma phenotype and the gene regulatory architecture at this locus. (J Allergy Clin Immunol 2018;142:749–64.)

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“… 5 We recently reported that T cells are increased in the lungs of IPF patients, and that subsets expressing specific chemokine receptors are associated with improved lung function. 6 Gene expression profiles in peripheral blood mononuclear cells from IPF patients also have implicated a role for T cells in protection. 7 In particular, low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicted decreased long-term transplant-free survival.…”

Section: Introductionmentioning

confidence: 99%

ICOS protects against mortality from acute lung injury through activation of IL-5+ ILC2s

et al. 2018

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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis. Of ICOS expressing cells, type 2 innate lymphocytes (ILC2s) are the first to respond to bleomycin-induced injury, and this expansion is ICOS-dependent. Interestingly, a similar decrease in ICOS+ ILCs was found in lung tissue from IPF patients. IL-5, produced primarily by ILC2s, was significantly reduced after lung injury in ICOS−/− mice, and strikingly, treatment with IL-5 protected both ICOS−/− and wild type mice from mortality. These results imply that low ICOS expression and decreased lung ILC2s in IPF patients may contribute to poor recovery from infections and acute exacerbation, and that IL-5 treatment may be a novel therapeutic strategy to overcome these defects and protect against lung injury.

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Skewed Lung CCR4 to CCR6 CD4+ T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function

Cited by 33 publications

References 55 publications

Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation

Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation

A decade of research on the 17q12-21 asthma locus: Piecing together the puzzle

ICOS protects against mortality from acute lung injury through activation of IL-5+ ILC2s

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