POU2AF1 functions in the human airway epithelium to regulate expression of host defense genes

Haixia Zhou, Angelika Brekman, Wu Lin Zuo, Xuemei Ou, Renat Shaykhiev, Francisco J. Agosto-Perez, Rui Wang, Matthew S. Walters, Jacqueline Salit, Yael Strulovici-Barel, Michelle R. Staudt, Robert J. Kaner, Jason G. Mezey, Ronald Crystal, Guoqing Wang

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3159-3167
Number of pages9
JournalJournal of Immunology
Volume196
Issue number7
DOIs
Publication statusPublished - 1 Apr 2016
Externally publishedYes

Fingerprint

Epithelium
Genes
Up-Regulation
HLA-DR alpha-Chains
Stem Cells
Lymphocytes
Lentivirus
Bronchoscopy
Smoke
Tobacco Products
Cell Differentiation
Interleukin-6
Clone Cells
Smoking
Immunohistochemistry
Observation
Genome
Staining and Labeling
Gene Expression
Lung

ASJC Scopus subject areas

  • Immunology

Cite this

Zhou, H., Brekman, A., Zuo, W. L., Ou, X., Shaykhiev, R., Agosto-Perez, F. J., ... Wang, G. (2016). POU2AF1 functions in the human airway epithelium to regulate expression of host defense genes. Journal of Immunology, 196(7), 3159-3167. https://doi.org/10.4049/jimmunol.1502400

POU2AF1 functions in the human airway epithelium to regulate expression of host defense genes. / Zhou, Haixia; Brekman, Angelika; Zuo, Wu Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J.; Wang, Rui; Walters, Matthew S.; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R.; Kaner, Robert J.; Mezey, Jason G.; Crystal, Ronald; Wang, Guoqing.

In: Journal of Immunology, Vol. 196, No. 7, 01.04.2016, p. 3159-3167.

Research output: Contribution to journalArticle

Zhou, H, Brekman, A, Zuo, WL, Ou, X, Shaykhiev, R, Agosto-Perez, FJ, Wang, R, Walters, MS, Salit, J, Strulovici-Barel, Y, Staudt, MR, Kaner, RJ, Mezey, JG, Crystal, R & Wang, G 2016, 'POU2AF1 functions in the human airway epithelium to regulate expression of host defense genes', Journal of Immunology, vol. 196, no. 7, pp. 3159-3167. https://doi.org/10.4049/jimmunol.1502400
Zhou, Haixia ; Brekman, Angelika ; Zuo, Wu Lin ; Ou, Xuemei ; Shaykhiev, Renat ; Agosto-Perez, Francisco J. ; Wang, Rui ; Walters, Matthew S. ; Salit, Jacqueline ; Strulovici-Barel, Yael ; Staudt, Michelle R. ; Kaner, Robert J. ; Mezey, Jason G. ; Crystal, Ronald ; Wang, Guoqing. / POU2AF1 functions in the human airway epithelium to regulate expression of host defense genes. In: Journal of Immunology. 2016 ; Vol. 196, No. 7. pp. 3159-3167.
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