Show simple item record

dc.contributor.authorGrumelli, Sandra
dc.contributor.authorLu, Bao
dc.contributor.authorPeterson, Leif
dc.contributor.authorMaeno, Toshitaka
dc.contributor.authorGerard, Craig John
dc.date.accessioned2011-12-05T02:38:15Z
dc.date.issued2011
dc.identifier.citationGrumelli, Sandra, Bao Lu, Leif Peterson, Toshitaka Maeno, and Craig Gerard. 2011. CD46 Protects against Chronic Obstructive Pulmonary Disease. PLoS ONE 6(5): e18785.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5360054
dc.description.abstractBackground: Chronic obstructive pulmonary disease and emphysema develops in 15% of ex-smokers despite sustained quitting, while 10% are free of emphysema or severe lung obstruction. The cause of the incapacity of the immune system to clear the inflammation in the first group remains unclear. Methods and Findings: We searched genes that were protecting ex-smokers without emphysema, using microarrays on portions of human lungs surgically removed; we found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a lower expression of CD46 and verified this finding by qRT-PCR and flow cytometry. Also, there was a significant association among decreased CD46\(^+\) cells with decreased CD4\(^+\)T cells, apoptosis mediator CD95 and increased CD8\(^+\)T cells that were protecting patients without emphysema or severe chronic obstructive pulmonary disease. CD46 not only regulates the production of T regulatory cells, which suppresses CD8\(^+\)T cell proliferation, but also the complement cascade by degradation of C3b. These results were replicated in the murine smoking model, which showed increased C5a (produced by C3b) that suppressed IL12 mediated bias to T helper 1 cells and elastin co-precipitation with C3b, suggesting that elastin could be presented as an antigen. Thus, using ELISA from elastin peptides, we verified that 43% of the patients with severe early onset of chronic obstructive pulmonary disease tested positive for IgG to elastin in their serum compared to healthy controls. Conclusions: These data suggest that higher expression of CD46 in the lungs of ex-smoker protects them from emphysema and chronic obstructive pulmonary disease by clearing the inflammation impeding the proliferation of CD8\(^+\) T cells and necrosis, achieved by production of T regulatory cells and degradation of C3b; restraining the complement cascade favors apoptosis over necrosis, protecting them from autoimmunity and chronic inflammation.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0018785en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089601/pdf/en_US
dash.licenseLAA
dc.subjectchronic obstructive pulmonary diseasesen_US
dc.subjectgenetics of diseaseen_US
dc.subjectclinical immunologyen_US
dc.subjectimmune responseen_US
dc.subjectimmunomodulationen_US
dc.titleCD46 Protects Against Chronic Obstructive Pulmonary Diseaseen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorLu, Bao
dc.date.available2011-12-05T02:38:15Z
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0018785*
dash.contributor.affiliatedLu, Bao
dash.contributor.affiliatedGerard, Craig John


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record