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...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| author | So-Eun Son Jung-Min Koh Dong-Soon Im |
| author_facet | So-Eun Son Jung-Min Koh Dong-Soon Im |
| author_sort | So-Eun Son |
| collection | DOAJ |
| description | 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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| spelling | doaj.art-bcc8598077274a26b6db31d721a0dd312023-11-23T08:17:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239448210.3390/ijms23094482Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in MiceSo-Eun Son0Jung-Min Koh1Dong-Soon Im2Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDivision of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDietary 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.https://www.mdpi.com/1422-0067/23/9/4482psoriasisimiquimodfree fatty acid receptor 4FFA4polyunsaturated fatty acidsIL-17 |
| spellingShingle | So-Eun Son Jung-Min Koh Dong-Soon Im Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in Mice International Journal of Molecular Sciences psoriasis imiquimod free fatty acid receptor 4 FFA4 polyunsaturated fatty acids IL-17 |
| title | Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in Mice |
| title_full | Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in Mice |
| title_fullStr | Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in Mice |
| title_full_unstemmed | Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in Mice |
| title_short | Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in Mice |
| title_sort | free fatty acid receptor 4 ffa4 activation ameliorates imiquimod induced psoriasis in mice |
| topic | psoriasis imiquimod free fatty acid receptor 4 FFA4 polyunsaturated fatty acids IL-17 |
| url | https://www.mdpi.com/1422-0067/23/9/4482 |
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