The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches
Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin (IL)-23/IL-17 axis. Patients with psoriasis manifest functional defects in CD4<sup>+</sup>CD25<sup>+</sup> forkhead box protein 3 (Foxp3)<sup>+</sup>...
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doaj-39c5465ae7794bc690ef880624c611272021-09-09T13:49:33ZengMDPI AGJournal of Clinical Medicine2077-03832021-08-01103880388010.3390/jcm10173880The Defect in Regulatory T Cells in Psoriasis and Therapeutic ApproachesNaoko Kanda0Toshihiko Hoashi1Hidehisa Saeki2Department of Dermatology, Nippon Medical School, Chiba Hokusoh Hospital, Inzai 270-1694, JapanDepartment of Dermatology, Nippon Medical School, Tokyo 113-8602, JapanDepartment of Dermatology, Nippon Medical School, Tokyo 113-8602, JapanPsoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin (IL)-23/IL-17 axis. Patients with psoriasis manifest functional defects in CD4<sup>+</sup>CD25<sup>+</sup> forkhead box protein 3 (Foxp3)<sup>+</sup> regulatory T cells (Tregs), which suppress the excess immune response and mediate homeostasis. Defects in Tregs contribute to the pathogenesis of psoriasis and may attribute to enhanced inhibition and/or impaired stimulation of Tregs. IL-23 induces the conversion of Tregs into type 17 helper T (Th17) cells. IL-17A reduces transforming growth factor (TGF)-β1 production, Foxp3 expression, and suppresses Treg activity. Short-chain fatty acids (SCFAs), butyrate, propionate, and acetate are microbiota-derived fermentation products that promote Treg development and function by inducing <i>Foxp3</i> expression or inducing dendritic cells or intestinal epithelial cells to produce retinoic acids or TGF-β1, respectively. The gut microbiome of patients with psoriasis revealed reduced SCFA-producing bacteria, <i>Bacteroidetes,</i> and <i>Faecallibacterium</i>, which may contribute to the defect in Tregs. Therapeutic agents currently used, viz., anti-IL-23p19 or anti-IL-17A antibodies, retinoids, vitamin D3, dimethyl fumarate, narrow-band ultraviolet B, or those under development for psoriasis, viz., signal transducer and activator of transcription 3 inhibitors, butyrate, histone deacetylase inhibitors, and probiotics/prebiotics restore the defected Tregs. Thus, restoration of Tregs is a promising therapeutic target for psoriasis.https://www.mdpi.com/2077-0383/10/17/3880psoriasisregulatory T cellforkhead box protein 3short chain fatty acidbutyrateinterleukin-17A |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Naoko Kanda Toshihiko Hoashi Hidehisa Saeki |
spellingShingle |
Naoko Kanda Toshihiko Hoashi Hidehisa Saeki The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches Journal of Clinical Medicine psoriasis regulatory T cell forkhead box protein 3 short chain fatty acid butyrate interleukin-17A |
author_facet |
Naoko Kanda Toshihiko Hoashi Hidehisa Saeki |
author_sort |
Naoko Kanda |
title |
The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches |
title_short |
The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches |
title_full |
The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches |
title_fullStr |
The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches |
title_full_unstemmed |
The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches |
title_sort |
defect in regulatory t cells in psoriasis and therapeutic approaches |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2021-08-01 |
description |
Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin (IL)-23/IL-17 axis. Patients with psoriasis manifest functional defects in CD4<sup>+</sup>CD25<sup>+</sup> forkhead box protein 3 (Foxp3)<sup>+</sup> regulatory T cells (Tregs), which suppress the excess immune response and mediate homeostasis. Defects in Tregs contribute to the pathogenesis of psoriasis and may attribute to enhanced inhibition and/or impaired stimulation of Tregs. IL-23 induces the conversion of Tregs into type 17 helper T (Th17) cells. IL-17A reduces transforming growth factor (TGF)-β1 production, Foxp3 expression, and suppresses Treg activity. Short-chain fatty acids (SCFAs), butyrate, propionate, and acetate are microbiota-derived fermentation products that promote Treg development and function by inducing <i>Foxp3</i> expression or inducing dendritic cells or intestinal epithelial cells to produce retinoic acids or TGF-β1, respectively. The gut microbiome of patients with psoriasis revealed reduced SCFA-producing bacteria, <i>Bacteroidetes,</i> and <i>Faecallibacterium</i>, which may contribute to the defect in Tregs. Therapeutic agents currently used, viz., anti-IL-23p19 or anti-IL-17A antibodies, retinoids, vitamin D3, dimethyl fumarate, narrow-band ultraviolet B, or those under development for psoriasis, viz., signal transducer and activator of transcription 3 inhibitors, butyrate, histone deacetylase inhibitors, and probiotics/prebiotics restore the defected Tregs. Thus, restoration of Tregs is a promising therapeutic target for psoriasis. |
topic |
psoriasis regulatory T cell forkhead box protein 3 short chain fatty acid butyrate interleukin-17A |
url |
https://www.mdpi.com/2077-0383/10/17/3880 |
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