Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes

Amanda S. Büchau, Daniel T. MacLeod, Shin Morizane, Paul F. Kotol, Tissa Hata, Richard L. Gallo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Innate immune responses involve the production of antimicrobial peptides (AMPs), chemokines, and cytokines. We report here the identification of B-cell leukemia (Bcl)-3 as a modulator of innate immune signaling in keratinocytes. In this study, it is shown that Bcl-3 is inducible by the Th2 cytokines IL-4 and IL-13 and is overexpressed in lesional skin of atopic dermatitis (AD) patients. Bcl-3 was shown to be important to cutaneous innate immune responses as silencing of Bcl-3 by small-interfering RNA (siRNA) reversed the downregulatory effect of IL-4 on the HBD3 expression. Bcl-3 silencing enhanced vitamin D3 (1,25D3)-induced gene expression of cathelicidin AMP in keratinocytes, suggesting a negative regulatory function on cathelicidin transcription. Furthermore, 1,25D3 suppressed Bcl-3 expression in vitro and in vivo. This study identified Bcl-3 as an important modulator of cutaneous innate immune responses and its possible therapeutic role in AD.

Original languageEnglish
Pages (from-to)2148-2155
Number of pages8
JournalJournal of Investigative Dermatology
Volume129
Issue number9
DOIs
Publication statusPublished - Sep 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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