Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in Mice
Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) has been used as an adjunct therapy for psoriasis due to its anti-inflammatory properties. Free fatty acid receptor 4 (FFA4 or GPR120) is a receptor-sensing n-3 PUFA. In the present study, we examined whether FFA4 acted as a the...
Main Authors: | , , |
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Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-04-01
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Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/23/9/4482 |
Summary: | Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) has been used as an adjunct therapy for psoriasis due to its anti-inflammatory properties. Free fatty acid receptor 4 (FFA4 or GPR120) is a receptor-sensing n-3 PUFA. In the present study, we examined whether FFA4 acted as a therapeutic target for n-3 PUFA in psoriasis therapy. Experimentally, psoriasis-like skin lesions were induced by treatment with imiquimod for 6 consecutive days. A selective FFA4 agonist, Compound A (30 mg/kg), was used in FFA4 WT and FFA4 KO mice. Imiquimod-induced psoriasis-like skin lesions, which present as erythematous papules and plaques with silver scaling, as well as markedly elevated IL-17/IL-23 cytokine levels in skin tissues, were significantly suppressed by Compound A in FFA4 WT mice, but not in FFA4 KO mice. Enlarged lymph nodes and spleens, as well as imiquimod-induced, elevated IL-17/IL-23 cytokine levels, were also strongly suppressed by Compound A in FFA4 WT mice, but not in FFA4 KO mice. Imiquimod-induced increases in the CD4<sup>+</sup>IL-17A<sup>+</sup> T cell population in lymph nodes and spleens were suppressed by Compound A treatment in FFA4 WT mice; however, this was not seen in FFA4 KO mice. Furthermore, compound A suppressed the differentiation of CD4<sup>+</sup> naïve T cells from splenocytes into T<sub>H</sub>17 cells in an FFA4-dependent manner. In conclusion, we demonstrated that the activation of FFA4 ameliorates imiquimod-induced psoriasis, and the suppression of the differentiation of T<sub>H</sub>17 cells may partly contribute to its efficacy. Therefore, we suggest that FFA4 could be a therapeutic target for psoriasis therapy. |
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ISSN: | 1661-6596 1422-0067 |