Format

Send to

Choose Destination
J Immunol. 2016 Apr 1;196(7):3159-67. doi: 10.4049/jimmunol.1502400. Epub 2016 Feb 29.

POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

Author information

1
Department of Respiratory Medicine, West China Hospital, Sichuan University, Sichuan 610041, China; Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
2
Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
3
Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College, New York, NY 10065; and.
4
Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065; Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, NY 14853.
5
Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College, New York, NY 10065; and geneticmedicine@med.cornell.edu.

Abstract

In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.

PMID:
26927796
PMCID:
PMC4799774
DOI:
10.4049/jimmunol.1502400
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center