2. Academic Validation
  3. The AhR-Ovol1-Id1 regulatory axis in keratinocytes promotes epidermal and immune homeostasis in atopic dermatitis-like skin inflammation

The AhR-Ovol1-Id1 regulatory axis in keratinocytes promotes epidermal and immune homeostasis in atopic dermatitis-like skin inflammation

  • Cell Mol Immunol. 2025 Mar;22(3):300-315. doi: 10.1038/s41423-025-01264-z.
Zeyu Chen 1 2 3 4,  Morgan Dragan 2 5,  Peng Sun 2 5,  Daniel Haensel 2 5,  Remy Vu 2 5,  Lian Cui 1 4,  Peiyao Zhu 1 4,  Nan Yang 1 4,  Yuling Shi 6 7,  Xing Dai 8 9 10
Affiliations

Affiliations

  • 1 Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
  • 2 Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, 92697, USA.
  • 3 Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
  • 4 Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
  • 5 The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA, 92697, USA.
  • 6 Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China. shiyuling1973@tongji.edu.cn.
  • 7 Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China. shiyuling1973@tongji.edu.cn.
  • 8 Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, 92697, USA. xdai@uci.edu.
  • 9 The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA, 92697, USA. xdai@uci.edu.
  • 10 Department of Dermatology, School of Medicine, University of California, Irvine, CA, 92697, USA. xdai@uci.edu.
PMID: 39939818 DOI: 10.1038/s41423-025-01264-z
Abstract

The skin is our outer permeability and immune defense barrier against myriad external assaults. Aryl Hydrocarbon Receptor (AhR) senses environmental factors and regulates barrier robustness and immune homeostasis. AhR agonists have been approved by the FDA for psoriasis treatment and are in clinical trials for the treatment of atopic dermatitis (AD), but the underlying mechanism of action remains poorly defined. Here, we report that OVOL1/Ovol1 is a conserved and direct transcriptional target of AhR in epidermal keratinocytes. We show that OVOL1/Ovol1 influences AhR-mediated regulation of keratinocyte gene expression and that OVOL1/Ovol1 ablation in keratinocytes impairs the barrier-promoting function of AhR, exacerbating AD-like inflammation. Mechanistically, we have identified Ovol1's direct downstream targets genome-wide and provided in vivo evidence supporting the role of Id1 as a functional target in barrier maintenance, disease suppression, and neutrophil accumulation. Furthermore, our findings reveal that an IL-1/dermal γδT cell axis exacerbates type 2 and 3 immune responses downstream of barrier perturbation in Ovol1-deficient AD skin. Finally, we present data suggesting the clinical relevance of OVOL1 and ID1 functions in human AD skin. Our study highlights a keratinocyte-intrinsic AhR-Ovol1-Id1 regulatory axis that promotes both epidermal and immune homeostasis in the context of skin inflammation, identifying new therapeutic targets.

Keywords

AhR; Atopic dermatitis; Epidermis; Gamma delta T; IL-1; Id1; Ovol1; Skin barrier; Skin inflammation; Transcription factor.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z