C5a/C5aR1 mediates the IMQ-induced psoriatic skin inflammation via promoting IL-17A expression by γδ T cells in mice
Objective To explore the effects and underlying mechanism of C5a/C5aR1 pathway in mediating imiquimod (IMQ)-induced psoriatic skin inflammation by increasing IL-17A expression in γδ T cells. Methods C5aR1+/+ and C5aR1-/- mice were treated with IMQ or control Vasline cream for 6 consecutive days. The...
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| Format: | Article |
| Language: | zho |
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Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.
2022-09-01
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| Series: | Jichu yixue yu linchuang |
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| Online Access: | http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-42-9-1325.pdf |
| _version_ | 1797365845075165184 |
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| author | ZHENG Quan-you, LIANG Shen-ju,SHU Yong, ZHOU Shan, ZHONG Yu, SHENG Fen, TANG Ming-jun |
| author_facet | ZHENG Quan-you, LIANG Shen-ju,SHU Yong, ZHOU Shan, ZHONG Yu, SHENG Fen, TANG Ming-jun |
| author_sort | ZHENG Quan-you, LIANG Shen-ju,SHU Yong, ZHOU Shan, ZHONG Yu, SHENG Fen, TANG Ming-jun |
| collection | DOAJ |
| description | Objective To explore the effects and underlying mechanism of C5a/C5aR1 pathway in mediating imiquimod (IMQ)-induced psoriatic skin inflammation by increasing IL-17A expression in γδ T cells. Methods C5aR1+/+ and C5aR1-/- mice were treated with IMQ or control Vasline cream for 6 consecutive days. The psoriatic skin inflammation was monitored. Inflammatory cells infiltration (T cells and neutrophils) and cytokines expression (IL-17A and TNF-α) were tested by immunohistochemistry (IHC). The percentages and cellular sources of IL-17A in both draining lymph nodes and skin lesions were analyzed by flow cytometry (FCM). Before IMQ application,C5aR1a peptide was injected into C5aR1+/+ mice and the psoriatic skin lesions as well as IL-17A expression were examined. Additionally, the isolated spleen lymphocytes were stimulated with C5a, IL23 or C5aR1a and then tested with FCM for the expression of IL-17A in γδ T cells. Results It was shown that C5aR1 deficiency clearly ameliorated IMQ induced psoriatic skin inflammation and was coupled with decreased keratinocytes proliferation, attenuated CD3 positive T cells and neutrophils, alleviated cytokines expression (IL-17A and TNF-α). FCM results indicated that C5aR1 loss significantly decreased the percentages of IL-17A positive cells in both draining lymph nodes and skin lesions, and γδ CD3+ TCR+ T cell was proved to be the major source of IL-17A. In consistent with that, blocking C5a/C5aR1 pathway with C5aR1a peptide remarkably alleviated IMQ induced skin lesions and IL-17A responses. Moreover, blocking C5a/C5aR1 with C5aR1a significantly down-regulated IL-17A expression in γδ T cells in vitro. Conclusions This study indicates that C5a/C5aR1 signaling plays an essential role in the pathogenesis of psoriatic lesions by enhancing IL-17A expression by γδ T cells. Blocking C5a/C5aR1 pathway is a promise strategy in the treatment of psoriasis patients. |
| first_indexed | 2024-03-08T16:54:48Z |
| format | Article |
| id | doaj.art-45590e7c53dc43f39954794fe9c36b31 |
| institution | Directory Open Access Journal |
| issn | 1001-6325 |
| language | zho |
| last_indexed | 2024-03-08T16:54:48Z |
| publishDate | 2022-09-01 |
| publisher | Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. |
| record_format | Article |
| series | Jichu yixue yu linchuang |
| spelling | doaj.art-45590e7c53dc43f39954794fe9c36b312024-01-05T02:36:18ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252022-09-014291325133210.16352/j.issn.1001-6325.2022.09.1325C5a/C5aR1 mediates the IMQ-induced psoriatic skin inflammation via promoting IL-17A expression by γδ T cells in miceZHENG Quan-you, LIANG Shen-ju,SHU Yong, ZHOU Shan, ZHONG Yu, SHENG Fen, TANG Ming-jun01. Department of Nephrology and Urology, the 958th Hospital of PLA Army, the First Affiliated Hospital, Army Medical University, Chongqing 400020;;2. Department of Rheumatism and Immunology, Army Medical Center of PLA, Chongqing 400042,ChinaObjective To explore the effects and underlying mechanism of C5a/C5aR1 pathway in mediating imiquimod (IMQ)-induced psoriatic skin inflammation by increasing IL-17A expression in γδ T cells. Methods C5aR1+/+ and C5aR1-/- mice were treated with IMQ or control Vasline cream for 6 consecutive days. The psoriatic skin inflammation was monitored. Inflammatory cells infiltration (T cells and neutrophils) and cytokines expression (IL-17A and TNF-α) were tested by immunohistochemistry (IHC). The percentages and cellular sources of IL-17A in both draining lymph nodes and skin lesions were analyzed by flow cytometry (FCM). Before IMQ application,C5aR1a peptide was injected into C5aR1+/+ mice and the psoriatic skin lesions as well as IL-17A expression were examined. Additionally, the isolated spleen lymphocytes were stimulated with C5a, IL23 or C5aR1a and then tested with FCM for the expression of IL-17A in γδ T cells. Results It was shown that C5aR1 deficiency clearly ameliorated IMQ induced psoriatic skin inflammation and was coupled with decreased keratinocytes proliferation, attenuated CD3 positive T cells and neutrophils, alleviated cytokines expression (IL-17A and TNF-α). FCM results indicated that C5aR1 loss significantly decreased the percentages of IL-17A positive cells in both draining lymph nodes and skin lesions, and γδ CD3+ TCR+ T cell was proved to be the major source of IL-17A. In consistent with that, blocking C5a/C5aR1 pathway with C5aR1a peptide remarkably alleviated IMQ induced skin lesions and IL-17A responses. Moreover, blocking C5a/C5aR1 with C5aR1a significantly down-regulated IL-17A expression in γδ T cells in vitro. Conclusions This study indicates that C5a/C5aR1 signaling plays an essential role in the pathogenesis of psoriatic lesions by enhancing IL-17A expression by γδ T cells. Blocking C5a/C5aR1 pathway is a promise strategy in the treatment of psoriasis patients.http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-42-9-1325.pdfpsoriasis| c5a/c5ar1 pathway| interleukin-17a(il-17a)| γδ t cells |
| spellingShingle | ZHENG Quan-you, LIANG Shen-ju,SHU Yong, ZHOU Shan, ZHONG Yu, SHENG Fen, TANG Ming-jun C5a/C5aR1 mediates the IMQ-induced psoriatic skin inflammation via promoting IL-17A expression by γδ T cells in mice Jichu yixue yu linchuang psoriasis| c5a/c5ar1 pathway| interleukin-17a(il-17a)| γδ t cells |
| title | C5a/C5aR1 mediates the IMQ-induced psoriatic skin inflammation via promoting IL-17A expression by γδ T cells in mice |
| title_full | C5a/C5aR1 mediates the IMQ-induced psoriatic skin inflammation via promoting IL-17A expression by γδ T cells in mice |
| title_fullStr | C5a/C5aR1 mediates the IMQ-induced psoriatic skin inflammation via promoting IL-17A expression by γδ T cells in mice |
| title_full_unstemmed | C5a/C5aR1 mediates the IMQ-induced psoriatic skin inflammation via promoting IL-17A expression by γδ T cells in mice |
| title_short | C5a/C5aR1 mediates the IMQ-induced psoriatic skin inflammation via promoting IL-17A expression by γδ T cells in mice |
| title_sort | c5a c5ar1 mediates the imq induced psoriatic skin inflammation via promoting il 17a expression by γδ t cells in mice |
| topic | psoriasis| c5a/c5ar1 pathway| interleukin-17a(il-17a)| γδ t cells |
| url | http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-42-9-1325.pdf |
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