Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes.
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.
Büchau
Amanda S
AS
Division of Dermatology, Department of Medicine, University of California, San Diego, VA San Diego Healthcare System, San Diego, California 92161, USA.
MacLeod
Daniel T
DT
Morizane
Shin
S
Kotol
Paul F
PF
Hata
Tissa
T
Gallo
Richard L
RL
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
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