Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia

Sun Mi Choi, Jeremy P. McAleer, Mingquan Zheng, Derek A. Pociask, Mark Kaplan, Shulin Qin, Todd A. Reinhart, Jay K. Kolls

Research output: Contribution to journalArticle

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Abstract

Pulmonary Staphylococcus aureus (SA) infections are a public health concern and a major complication of hyper-IgE syndrome, caused by mutations in STAT3. In contrast to previous findings of skin infection, we observed that clearance of SA from the lung did not require T, B, or NK cells but did require Stat3 activation. Immunohistochemistry showed robust Stat3 phosphorylation in the lung epithelium. We identified that a critical Stat3 target gene in lung epithelium is Reg3g (regenerating islet-derived 3 γ), a gene which is highly expressed in gastrointestinal epithelium but whose role in pulmonary host defense is uncharacterized. Stat3 regulated Reg3g transcription through direct binding at the Reg3g promoter region. Recombinant Reg3γ bound to SA and had both bacteriostatic and bactericidal activity in a dose-dependent fashion. Stat3 inhibition in vivo reduced Reg3g transcripts in the lung, and more importantly, recombinant Reg3γ rescued mice from defective SA clearance. These findings reveal an antibacterial function for lung epithelium through Stat3-mediated induction of Reg3γ.

Original languageEnglish
Pages (from-to)551-561
Number of pages11
JournalJournal of Experimental Medicine
Volume210
Issue number3
DOIs
StatePublished - 2013

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Methicillin-Resistant Staphylococcus aureus
Pneumonia
Lung
Staphylococcus aureus
Epithelium
Proteins
Job Syndrome
Infection
Genetic Promoter Regions
Natural Killer Cells
Genes
B-Lymphocytes
Public Health
Immunohistochemistry
Phosphorylation
Skin
Mutation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia. / Choi, Sun Mi; McAleer, Jeremy P.; Zheng, Mingquan; Pociask, Derek A.; Kaplan, Mark; Qin, Shulin; Reinhart, Todd A.; Kolls, Jay K.

In: Journal of Experimental Medicine, Vol. 210, No. 3, 2013, p. 551-561.

Research output: Contribution to journalArticle

Choi, Sun Mi ; McAleer, Jeremy P. ; Zheng, Mingquan ; Pociask, Derek A. ; Kaplan, Mark ; Qin, Shulin ; Reinhart, Todd A. ; Kolls, Jay K. / Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia. In: Journal of Experimental Medicine. 2013 ; Vol. 210, No. 3. pp. 551-561.
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AU - Reinhart, Todd A.

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