Serum amyloid A/anti-CCL20 induced the rebalance of Th17/regulatory T cells in SodA-induced sarcoidosis
Copyright © 2022 Elsevier B.V. All rights reserved..
Sarcoidosis is a multisystemic granulomatous inflammation associated with Th17/regulatory T cell (Treg) polarization. As a marker of inflammation, serum amyloid A (SAA) could upregulate the expression of chemokine ligand 20 (CCL20), which induces the migration of Treg cells and Th17 cells by binding and activating thechemokine C-C receptor (CCR) 6. Our goal was to determine whether SAA/anti-CCL20 induces Th17/Treg rebalance in pulmonary sarcoidosis. The deposition of SAA- and Th17/Treg-related proteins in SodA-induced granulomas was tested using immunohistochemistry. Mice with SodA-induced sarcoidosis were treated with SAA or SAA + anti-CCL20, and then Th1/Th2 and Th17/Treg cells were detected by fluorescence-activated cell sorting (FACS) analysis. The expression of SAA/CCL20 and IL-23/IL-17A was detected by enzyme-linked immunosorbent assay (ELISA) and multiplex. Key proteins in the TGF-β/Smad signaling pathway were tested by western blot. SAA mainly plays a pro-inflammatory role by promoting the expression of CCL20 and IL-17A in bronchoalveolar lavage fluid (BALF) and serum, exacerbating this elevation of CD4+/CD8+ T cells in both mediastinal lymph nodes (LNs) and BALF, as well as proliferating Th1 in LNs in SodA-induced pulmonary sarcoidosis. In addition, SAA could also promote the proliferation of Tregs in LNs. Intriguingly, blocking of CCL20 could partially reverse the expression of Th17-related cytokine, ameliorate Th1/Th2 and Treg/Th17 bias in mice with SodA-induced pulmonary sarcoidosis, and rescue the overactivation of the TGF-β/Smad2/Smad3 signaling pathway. Anti-CCL20 may have the potential for therapeutic translation, targeting on the immunopathogenesis of pulmonary sarcoidosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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| Enthalten in: |
International immunopharmacology - 109(2022) vom: 15. Aug., Seite 108784 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Meng, Kaifang [VerfasserIn] |
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| Links: |
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| Themen: |
Chemokine ligand 20 |
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| Anmerkungen: |
Date Completed 21.06.2022 Date Revised 21.06.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2022.108784 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM339902817 |
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| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a Sarcoidosis is a multisystemic granulomatous inflammation associated with Th17/regulatory T cell (Treg) polarization. As a marker of inflammation, serum amyloid A (SAA) could upregulate the expression of chemokine ligand 20 (CCL20), which induces the migration of Treg cells and Th17 cells by binding and activating thechemokine C-C receptor (CCR) 6. Our goal was to determine whether SAA/anti-CCL20 induces Th17/Treg rebalance in pulmonary sarcoidosis. The deposition of SAA- and Th17/Treg-related proteins in SodA-induced granulomas was tested using immunohistochemistry. Mice with SodA-induced sarcoidosis were treated with SAA or SAA + anti-CCL20, and then Th1/Th2 and Th17/Treg cells were detected by fluorescence-activated cell sorting (FACS) analysis. The expression of SAA/CCL20 and IL-23/IL-17A was detected by enzyme-linked immunosorbent assay (ELISA) and multiplex. Key proteins in the TGF-β/Smad signaling pathway were tested by western blot. SAA mainly plays a pro-inflammatory role by promoting the expression of CCL20 and IL-17A in bronchoalveolar lavage fluid (BALF) and serum, exacerbating this elevation of CD4+/CD8+ T cells in both mediastinal lymph nodes (LNs) and BALF, as well as proliferating Th1 in LNs in SodA-induced pulmonary sarcoidosis. In addition, SAA could also promote the proliferation of Tregs in LNs. Intriguingly, blocking of CCL20 could partially reverse the expression of Th17-related cytokine, ameliorate Th1/Th2 and Treg/Th17 bias in mice with SodA-induced pulmonary sarcoidosis, and rescue the overactivation of the TGF-β/Smad2/Smad3 signaling pathway. Anti-CCL20 may have the potential for therapeutic translation, targeting on the immunopathogenesis of pulmonary sarcoidosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chemokine ligand 20 | |
| 650 | 4 | |a Regulatory T cells | |
| 650 | 4 | |a Sarcoidosis | |
| 650 | 4 | |a Serum amyloid A | |
| 650 | 4 | |a T helper 17 cells | |
| 650 | 7 | |a Chemokines |2 NLM | |
| 650 | 7 | |a Interleukin-17 |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Serum Amyloid A Protein |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 700 | 1 | |a Zhang, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Chengxing |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Qianqian |e verfasserin |4 aut | |
| 700 | 1 | |a Gui, Xianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaoqin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Yanting |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Jingjing |e verfasserin |4 aut | |
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