Epidermal loss of Bcl6 exacerbates MC903-induced atopic dermatitis-like skin inflammation

• Published in: Biochemical and biophysical research communications 2024-04, Vol.705, p.149745, Article 149745
• Main Authors: Kanemaru, Kaori, Nagasawa, Kento, Kunugi, Yuta, Tanaka, Asahi, Ikeoku, Shunsuke, Tai, Yuki, Harada, Yohsuke, Nakamura, Yoshikazu
• Format: Article
• Language: English
• Subjects: Adherence junction; Animals; Atopic dermatitis; Bcl6; Calcitriol - analogs & derivatives; Cytokines - metabolism; Dermatitis, Atopic; Differentiation; Epidermis - metabolism; Inflammation - pathology; Keratinocyte; Keratinocytes - metabolism; Mice; Proto-Oncogene Proteins c-bcl-6 - metabolism; Skin - metabolism
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.149745

Atopic dermatitis (AD) is a chronic inflammatory skin disease where Th2-type immune responses are dominant. In the lesional skin of AD, keratinocytes show differentiation defects and secrete proinflammatory cytokines and chemokines, amplifying Th2-type responses in AD. We previously reported that inducible loss of B-cell lymphoma 6 (Bcl6), a transcription repressor and a master transcriptional regulator of follicular helper T cells and germinal center B cells, in the whole body results in upregulation of Th2-related cytokines in mouse skin. However, the role of Bcl6 in keratinocytes remains to be clarified. Here, we observed that BCL6 positively regulates the expression of keratinocyte differentiation markers and plasma membrane localization of adherence junctional proteins in keratinocyte cell culture. Although keratinocyte-specific loss of Bcl6 alone did not induce AD-like skin inflammation, it aggravates MC903-induced AD-like skin inflammation in mice. In addition, Bcl6 expression is decreased in the epidermis of lesional skin from MC903-induced AD-like skin inflammation in mice. These results strongly suggest that Bcl6 downregulation in keratinocytes contributes to the development and aggravation of AD-like skin inflammation in mice. •BCL6 inhibition impairs the induction of keratinocyte differentiation markers.•BCL6 plays a positive role in adherence junction formation in keratinocytes.•Epidermal loss of Bcl6 aggravates atopic dermatitis-like skin inflammation in mice.•Bcl6 expression decreases in atopic dermatitis-like skin lesions in mice.