NLRP3 deficiency aggravated DNFB-induced chronic itch by enhancing type 2 immunity IL-4/TSLP-TRPA1 axis in mice
BackgroundThe nod-like receptor family pyrin domain-containing 3 (NLRP3) has been implicated in various skin diseases. However, its role in mediating 2, 4-dinitrofluorobenzene (DNFB)-induced chronic itch remains unclear.MethodsWidetype (WT) and Nlrp3 deletion (Nlrp3-/-)mice, the expression of transi...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450887/full |
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| author | Si-Ting Huang Zuo-Ming Chen Zhe Peng Yu Wang Fan Yang Yang Tang Zi Li Li Wan Li Wan |
| author_facet | Si-Ting Huang Zuo-Ming Chen Zhe Peng Yu Wang Fan Yang Yang Tang Zi Li Li Wan Li Wan |
| author_sort | Si-Ting Huang |
| collection | DOAJ |
| description | BackgroundThe nod-like receptor family pyrin domain-containing 3 (NLRP3) has been implicated in various skin diseases. However, its role in mediating 2, 4-dinitrofluorobenzene (DNFB)-induced chronic itch remains unclear.MethodsWidetype (WT) and Nlrp3 deletion (Nlrp3-/-)mice, the expression of transient receptor potential (TRP) ankyrin 1 (TRPA1) inhibitor or recombinant mice interleukin-18 (IL-18) were used to establish and evaluate the severity of DNFB-mediated chronic itch. Quantitative real-time PCR, western blotting, immunohistochemistry staining, immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA) was used to examine the expression of NLRP3 inflammasome, type 2 immunity and receptors in dorsal root ganglion (DRG) neurons related with chronic itch. Flow cytometry was performed to quantify the frequency of type 2 immune cells.ResultsThis study revealed that the NLRP3 inflammasome was activated in the skin of DNFB-induced chronic itch mice. Surprisingly, the absence of Nlrp3 exacerbated itch behavior. In Nlrp3-/- mice, IL-18 expression was downregulated, whereas markers of type 2 immunity, such as IL-4 and thymic stromal lymphopoietin (TSLP), were significantly upregulated in the skin. Furthermore, TRPA1 and its colocalization with the IL-4 receptor were increased in the DRG. Inhibition of TRPA1 or administration of recombinant IL-18 significantly reduced DNFB-induced itch behavior in Nlrp3-/- mice. Recombinant IL-18 also decreased the expression of TRPA1, IL-4, and TSLP.DiscussionThese findings suggested that the absence of Nlrp3 aggravated DNFB-induced chronic itch by exacerbating type 2 immunity in the skin and enhancing the IL-4/TSLP-TRPA1 axis, potentially driven by reduced IL-18 levels. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-a7a6fe0ee470430eb7c6f546b62d3fbc2025-01-10T08:44:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14508871450887NLRP3 deficiency aggravated DNFB-induced chronic itch by enhancing type 2 immunity IL-4/TSLP-TRPA1 axis in miceSi-Ting Huang0Zuo-Ming Chen1Zhe Peng2Yu Wang3Fan Yang4Yang Tang5Zi Li6Li Wan7Li Wan8Department of Pain Management, The State Key Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pain Management, The State Key Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pain Management, The State Key Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pain Management, The State Key Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pain Management, The State Key Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pain Management, The State Key Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pain Management, The State Key Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaStem Cell Translational Medicine Center, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaBackgroundThe nod-like receptor family pyrin domain-containing 3 (NLRP3) has been implicated in various skin diseases. However, its role in mediating 2, 4-dinitrofluorobenzene (DNFB)-induced chronic itch remains unclear.MethodsWidetype (WT) and Nlrp3 deletion (Nlrp3-/-)mice, the expression of transient receptor potential (TRP) ankyrin 1 (TRPA1) inhibitor or recombinant mice interleukin-18 (IL-18) were used to establish and evaluate the severity of DNFB-mediated chronic itch. Quantitative real-time PCR, western blotting, immunohistochemistry staining, immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA) was used to examine the expression of NLRP3 inflammasome, type 2 immunity and receptors in dorsal root ganglion (DRG) neurons related with chronic itch. Flow cytometry was performed to quantify the frequency of type 2 immune cells.ResultsThis study revealed that the NLRP3 inflammasome was activated in the skin of DNFB-induced chronic itch mice. Surprisingly, the absence of Nlrp3 exacerbated itch behavior. In Nlrp3-/- mice, IL-18 expression was downregulated, whereas markers of type 2 immunity, such as IL-4 and thymic stromal lymphopoietin (TSLP), were significantly upregulated in the skin. Furthermore, TRPA1 and its colocalization with the IL-4 receptor were increased in the DRG. Inhibition of TRPA1 or administration of recombinant IL-18 significantly reduced DNFB-induced itch behavior in Nlrp3-/- mice. Recombinant IL-18 also decreased the expression of TRPA1, IL-4, and TSLP.DiscussionThese findings suggested that the absence of Nlrp3 aggravated DNFB-induced chronic itch by exacerbating type 2 immunity in the skin and enhancing the IL-4/TSLP-TRPA1 axis, potentially driven by reduced IL-18 levels.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450887/fullDNFB-induced chronic itchNlrp3 inflammasometype 2 immunityTRPA1IL-18 |
| spellingShingle | Si-Ting Huang Zuo-Ming Chen Zhe Peng Yu Wang Fan Yang Yang Tang Zi Li Li Wan Li Wan NLRP3 deficiency aggravated DNFB-induced chronic itch by enhancing type 2 immunity IL-4/TSLP-TRPA1 axis in mice Frontiers in Immunology DNFB-induced chronic itch Nlrp3 inflammasome type 2 immunity TRPA1 IL-18 |
| title | NLRP3 deficiency aggravated DNFB-induced chronic itch by enhancing type 2 immunity IL-4/TSLP-TRPA1 axis in mice |
| title_full | NLRP3 deficiency aggravated DNFB-induced chronic itch by enhancing type 2 immunity IL-4/TSLP-TRPA1 axis in mice |
| title_fullStr | NLRP3 deficiency aggravated DNFB-induced chronic itch by enhancing type 2 immunity IL-4/TSLP-TRPA1 axis in mice |
| title_full_unstemmed | NLRP3 deficiency aggravated DNFB-induced chronic itch by enhancing type 2 immunity IL-4/TSLP-TRPA1 axis in mice |
| title_short | NLRP3 deficiency aggravated DNFB-induced chronic itch by enhancing type 2 immunity IL-4/TSLP-TRPA1 axis in mice |
| title_sort | nlrp3 deficiency aggravated dnfb induced chronic itch by enhancing type 2 immunity il 4 tslp trpa1 axis in mice |
| topic | DNFB-induced chronic itch Nlrp3 inflammasome type 2 immunity TRPA1 IL-18 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450887/full |
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