IL‐23/IL‐17 immune axis mediates the imiquimod‐induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF‐κB pathway in macrophages and keratinocytes
Abstract The interleukin‐23 (IL‐23)/IL‐17 immune axis has been linked to the pathology of psoriasis, but how this axis contributes to skin inflammation in this disease remains unclear. We measured inflammatory cytokines associated with the IL‐23/IL‐17 immune axis in the serum of patients with psoria...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-08-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12683 |
| _version_ | 1797744309246623744 |
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| author | Wen‐Cheng Chen Chang‐Hui Wen Meng Wang Zi‐Dan Xiao Zhong‐Zhao Zhang Chun‐Lan Wu Ran Wu |
| author_facet | Wen‐Cheng Chen Chang‐Hui Wen Meng Wang Zi‐Dan Xiao Zhong‐Zhao Zhang Chun‐Lan Wu Ran Wu |
| author_sort | Wen‐Cheng Chen |
| collection | DOAJ |
| description | Abstract The interleukin‐23 (IL‐23)/IL‐17 immune axis has been linked to the pathology of psoriasis, but how this axis contributes to skin inflammation in this disease remains unclear. We measured inflammatory cytokines associated with the IL‐23/IL‐17 immune axis in the serum of patients with psoriasis using enzyme‐linked immunosorbent assays. Psoriasis was induced in male C57BL/6J mice using imiquimod (IMQ) cream, and animals received intraperitoneal injections of recombinant mouse anti‐IL‐23A or anti‐IL‐17A antibodies for 7 days. The potential effects of the IL‐23/IL‐17 immune axis on skin inflammation were assessed based on pathology scoring, hematoxylin–eosin staining of skin samples, and quantitation of inflammatory cytokines. Western blotting was used to evaluate levels of the following factors in skin: ACT1, TRAF6, TAK1, NF‐κB, and pNF‐κB. The serum of psoriasis patients showed elevated levels of several cytokines involved in the IL‐23/IL‐17 immune axis: IL‐2, IL‐4, IL‐8, IL‐12, IL‐17, IL‐22, IL‐23, and interferon‐γ. Levels of IL‐23p19 and IL‐17 were increased in serum and skin of IMQ‐treated mice, while ACT1, TRAF6, TAK1, NF‐κB, and pNF‐κB were upregulated in the skin. A large proportion of NF‐κB p65 localized in nucleus of involucrin+ cells in the epidermis and in F4/80+ cells of the dermis of psoriatic lesional skin. Treating these animals with anti‐IL‐23 or anti‐IL‐17 antibodies improved pathological score and immune imbalance, mitigated skin inflammation and downregulated ACT1, TRAF6, TAK1, NF‐κB, and pNF‐κB in skin. Our results suggest that skin inflammation mediated by the IL‐23/IL‐17 immune axis in psoriasis involves activation of the ACT1/TRAF6/TAK1/NF‐κB pathway in keratinocytes and macrophage. |
| first_indexed | 2024-03-12T15:07:54Z |
| format | Article |
| id | doaj.art-1008085a5d0545509eb2e3e021e48343 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-03-12T15:07:54Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-1008085a5d0545509eb2e3e021e483432023-08-12T03:36:47ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502023-08-0139878980010.1002/kjm2.12683IL‐23/IL‐17 immune axis mediates the imiquimod‐induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF‐κB pathway in macrophages and keratinocytesWen‐Cheng Chen0Chang‐Hui Wen1Meng Wang2Zi‐Dan Xiao3Zhong‐Zhao Zhang4Chun‐Lan Wu5Ran Wu6Department of Dermatology First Clinical Medical College, Guizhou University of Traditional Chinese Medicine Guiyang ChinaDepartment of Dermatology First Clinical Medical College, Guizhou University of Traditional Chinese Medicine Guiyang ChinaDepartment of Dermatology First Clinical Medical College, Guizhou University of Traditional Chinese Medicine Guiyang ChinaDepartment of Dermatology First Clinical Medical College, Guizhou University of Traditional Chinese Medicine Guiyang ChinaDepartment of Dermatology First Clinical Medical College, Guizhou University of Traditional Chinese Medicine Guiyang ChinaDepartment of Dermatology First Clinical Medical College, Guizhou University of Traditional Chinese Medicine Guiyang ChinaDepartment of Dermatology First Clinical Medical College, Guizhou University of Traditional Chinese Medicine Guiyang ChinaAbstract The interleukin‐23 (IL‐23)/IL‐17 immune axis has been linked to the pathology of psoriasis, but how this axis contributes to skin inflammation in this disease remains unclear. We measured inflammatory cytokines associated with the IL‐23/IL‐17 immune axis in the serum of patients with psoriasis using enzyme‐linked immunosorbent assays. Psoriasis was induced in male C57BL/6J mice using imiquimod (IMQ) cream, and animals received intraperitoneal injections of recombinant mouse anti‐IL‐23A or anti‐IL‐17A antibodies for 7 days. The potential effects of the IL‐23/IL‐17 immune axis on skin inflammation were assessed based on pathology scoring, hematoxylin–eosin staining of skin samples, and quantitation of inflammatory cytokines. Western blotting was used to evaluate levels of the following factors in skin: ACT1, TRAF6, TAK1, NF‐κB, and pNF‐κB. The serum of psoriasis patients showed elevated levels of several cytokines involved in the IL‐23/IL‐17 immune axis: IL‐2, IL‐4, IL‐8, IL‐12, IL‐17, IL‐22, IL‐23, and interferon‐γ. Levels of IL‐23p19 and IL‐17 were increased in serum and skin of IMQ‐treated mice, while ACT1, TRAF6, TAK1, NF‐κB, and pNF‐κB were upregulated in the skin. A large proportion of NF‐κB p65 localized in nucleus of involucrin+ cells in the epidermis and in F4/80+ cells of the dermis of psoriatic lesional skin. Treating these animals with anti‐IL‐23 or anti‐IL‐17 antibodies improved pathological score and immune imbalance, mitigated skin inflammation and downregulated ACT1, TRAF6, TAK1, NF‐κB, and pNF‐κB in skin. Our results suggest that skin inflammation mediated by the IL‐23/IL‐17 immune axis in psoriasis involves activation of the ACT1/TRAF6/TAK1/NF‐κB pathway in keratinocytes and macrophage.https://doi.org/10.1002/kjm2.12683interleukin 17interleukin 23NF‐κBpsoriasisskin inflammation |
| spellingShingle | Wen‐Cheng Chen Chang‐Hui Wen Meng Wang Zi‐Dan Xiao Zhong‐Zhao Zhang Chun‐Lan Wu Ran Wu IL‐23/IL‐17 immune axis mediates the imiquimod‐induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF‐κB pathway in macrophages and keratinocytes Kaohsiung Journal of Medical Sciences interleukin 17 interleukin 23 NF‐κB psoriasis skin inflammation |
| title | IL‐23/IL‐17 immune axis mediates the imiquimod‐induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF‐κB pathway in macrophages and keratinocytes |
| title_full | IL‐23/IL‐17 immune axis mediates the imiquimod‐induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF‐κB pathway in macrophages and keratinocytes |
| title_fullStr | IL‐23/IL‐17 immune axis mediates the imiquimod‐induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF‐κB pathway in macrophages and keratinocytes |
| title_full_unstemmed | IL‐23/IL‐17 immune axis mediates the imiquimod‐induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF‐κB pathway in macrophages and keratinocytes |
| title_short | IL‐23/IL‐17 immune axis mediates the imiquimod‐induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF‐κB pathway in macrophages and keratinocytes |
| title_sort | il 23 il 17 immune axis mediates the imiquimod induced psoriatic inflammation by activating act1 traf6 tak1 nf κb pathway in macrophages and keratinocytes |
| topic | interleukin 17 interleukin 23 NF‐κB psoriasis skin inflammation |
| url | https://doi.org/10.1002/kjm2.12683 |
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