title: Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes.
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.
authors.affiliation: Division of Dermatology, Department of Medicine, University of California, San Diego, VA San Diego Healthcare System, San Diego, California 92161, USA.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Büchau
authors.forename: Daniel T
authors.initials: DT
authors.lastname: MacLeod
authors.forename: Shin
authors.initials: S
authors.lastname: Morizane
authors.forename: Paul F
authors.initials: PF
authors.lastname: Kotol
authors.forename: Tissa
authors.initials: T
authors.lastname: Hata
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000502:physiology; D000081242:B-Cell Lymphoma 3 Protein; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D015603:Keratinocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D052002:NF-kappa B p50 Subunit / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D054804:Cathelicidins
chemical_list: C116777:1,25-dihydroxy-16,23-diene vitamin D3; D023181:Antimicrobial Cationic Peptides; D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D018793:Interleukin-13; D015850:Interleukin-6; D016209:Interleukin-8; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D002762:Cholecalciferol; D015847:Interleukin-4; D054804:Cathelicidins