2. Academic Validation
  3. Human β-defensin-3 attenuates atopic dermatitis-like inflammation through autophagy activation and the aryl hydrocarbon receptor signaling pathway

Human β-defensin-3 attenuates atopic dermatitis-like inflammation through autophagy activation and the aryl hydrocarbon receptor signaling pathway

  • J Clin Invest. 2022 Sep 1;132(17):e156501. doi: 10.1172/JCI156501.
Ge Peng 1 2,  Saya Tsukamoto 1 2,  Risa Ikutama 1 2,  Hai Le Thanh Nguyen 1 2,  Yoshie Umehara 1,  Juan V Trujillo-Paez 1,  Hainan Yue 1 2,  Miho Takahashi 1 2,  Takasuke Ogawa 2,  Ryoma Kishi 3 4,  Mitsutoshi Tominaga 3,  Kenji Takamori 3 4,  Jiro Kitaura 1,  Shun Kageyama 5,  Masaaki Komatsu 5,  Ko Okumura 1,  Hideoki Ogawa 1,  Shigaku Ikeda 1 2,  François Niyonsaba 1 6
Affiliations

Affiliations

  • 1 Atopy (Allergy) Research Center and.
  • 2 Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 3 Juntendo Itch Research Center, Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Japan.
  • 4 Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Japan.
  • 5 Department of Physiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 6 Faculty of International Liberal Arts, Juntendo University, Tokyo, Japan.
PMID: 35834333 DOI: 10.1172/JCI156501
Abstract

Human β-defensin-3 (hBD-3) exhibits antimicrobial and immunomodulatory activities; however, its contribution to Autophagy regulation remains unclear, and the role of Autophagy in the regulation of the epidermal barrier in atopic dermatitis (AD) is poorly understood. Here, keratinocyte Autophagy was restrained in the skin lesions of patients with AD and murine models of AD. Interestingly, hBD-3 alleviated the IL-4- and IL-13-mediated impairment of the tight junction (TJ) barrier through keratinocyte Autophagy activation, which involved Aryl Hydrocarbon Receptor (AhR) signaling. While Autophagy deficiency impaired the epidermal barrier and exacerbated inflammation, hBD-3 attenuated skin inflammation and enhanced the TJ barrier in AD. Importantly, hBD-3-mediated improvement of the TJ barrier was abolished in autophagy-deficient AD mice and in AhR-suppressed AD mice, suggesting a role for hBD-3-mediated Autophagy in the regulation of the epidermal barrier and inflammation in AD. Thus, Autophagy contributes to the pathogenesis of AD, and hBD-3 could be used for therapeutic purposes.

Keywords

Autophagy; Defensins; Dermatology; Inflammation; Tight junctions.

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