2. Academic Validation
  3. Bile Acids Improve Psoriasiform Dermatitis through Inhibition of IL-17A Expression and CCL20-CCR6-Mediated Trafficking of T Cells

Bile Acids Improve Psoriasiform Dermatitis through Inhibition of IL-17A Expression and CCL20-CCR6-Mediated Trafficking of T Cells

  • J Invest Dermatol. 2022 May;142(5):1381-1390.e11. doi: 10.1016/j.jid.2021.10.027.
Zhenrui Shi 1,  Xuesong Wu 2,  Chun-Yi Wu 3,  Satya P Singh 4,  Timothy Law 2,  Daisuke Yamada 2,  Mindy Huynh 2,  William Liakos 2,  Guiyan Yang 5,  Joshua M Farber 4,  Yu-Jui Yvonne Wan 5,  Samuel T Hwang 6
Affiliations

Affiliations

  • 1 Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, California, USA.
  • 2 Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, California, USA.
  • 3 Department of Neurology, School of Medicine, University of California, Davis, Sacramento, California, USA; UC Davis Bioanalysis and Pharmacokinetics Core facility, Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Sacramento, California, USA.
  • 4 Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • 5 Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, California, USA.
  • 6 Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, California, USA. Electronic address: [email protected].
PMID: 34808237 DOI: 10.1016/j.jid.2021.10.027
Abstract

Bile acids (BAs), produced in the liver and further transformed in the gut, are cholesterol-derived molecules involved in essential physiological processes. Recent studies suggest that BAs regulate T helper 17 cell function, but the underlying mechanism of this action and their therapeutic value in disease models remains unclear. Using an IL-23 minicircle DNA-based murine model of psoriasiform dermatitis, we showed that oral administration of secondary BAs, including lithocholic acid (LCA), deoxycholic acid, and 3-oxoLCA, significantly improved psoriasiform dermatitis without inducing apparent hepatotoxicity. Of the BAs tested, LCA possessed the greatest potency in treating psoriasiform dermatitis. Intravenous administration of LCA at a much lower dosage (compared with oral treatment) showed a comparable antipsoriatic effect and markedly suppressed the IL-17A response. Ex vivo experiments revealed that LCA reduced IL-17A production in IL-23-stimulated murine T cells in the absence of BA receptors TGR5 or FXR. Strikingly, BAs inhibited CCL20 expression in keratinocytes, which led to reduced migration of CCR6-expressing Jurkat cells cultured in the conditioned medium of stimulated keratinocytes. Thus, BAs improve psoriasiform dermatitis with minimal toxicity via direct inhibition of IL-17A production and blockade of CCL20-mediated trafficking, supporting the potential use of BAs in psoriasis.

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