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

Publication TypeJournal Article
Year of Publication2016
AuthorsZhou H, Brekman A, Zuo W-L, Ou X, Shaykhiev R, Agosto-Perez FJ, Wang R, Walters MS, Salit J, Strulovici-Barel Y, Staudt MR, Kaner RJ, Mezey JG, Crystal RG, Wang G
JournalJ Immunol
Date Published2016 Apr 01
KeywordsCell Differentiation, Cluster Analysis, Epithelial Cells, Gene Expression Profiling, Gene Expression Regulation, Humans, Immunity, Respiratory Mucosa, Smoking, Trans-Activators

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.

Alternate JournalJ. Immunol.
PubMed ID26927796
PubMed Central IDPMC4799774
Grant ListP20 HL113443 / HL / NHLBI NIH HHS / United States
T32 HL094284 / HL / NHLBI NIH HHS / United States
R01 HL107882 / HL / NHLBI NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UL1 RR0204143 / RR / NCRR NIH HHS / United States