Antisense oligonucleotides targeting IRF4 alleviate psoriasis
Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4+ (CD4+) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A...
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Elsevier
2025-07-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383525003107 |
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| author | Yanxia Yu Yirui Wang Weiwei Chen Chang Zhang Zhuo li Jing Yu Minhao Wang Can Song Sihao Yan Jiayi Lu Liangdan Sun |
| author_facet | Yanxia Yu Yirui Wang Weiwei Chen Chang Zhang Zhuo li Jing Yu Minhao Wang Can Song Sihao Yan Jiayi Lu Liangdan Sun |
| author_sort | Yanxia Yu |
| collection | DOAJ |
| description | Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4+ (CD4+) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A–IRF4–EP300–RORC–IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4−/− gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4+ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy. |
| format | Article |
| id | doaj-art-a8023bcd68924d2a9c5836f92168ec3c |
| institution | Matheson Library |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-a8023bcd68924d2a9c5836f92168ec3c2025-07-09T04:32:14ZengElsevierActa Pharmaceutica Sinica B2211-38352025-07-0115735753590Antisense oligonucleotides targeting IRF4 alleviate psoriasisYanxia Yu0Yirui Wang1Weiwei Chen2Chang Zhang3Zhuo li4Jing Yu5Minhao Wang6Can Song7Sihao Yan8Jiayi Lu9Liangdan Sun10Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei 230032, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Department of Dermatology, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China; School of Public Health, North China University of Science and Technology, Tangshan 063210, China; Health Science Center, North China University of Science and Technology, Tangshan 063210, China; Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei 230032, China; Hebei Key Laboratory of Medical Engineering and Integrated Utilization of Saline Alkali Land, Tangshan 063210, China; Hebei Administration of TCM Key Laboratory of Quality Control of Salt Alkali Resistant TCM, Tangshan 063210, China; Corresponding author.Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4+ (CD4+) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A–IRF4–EP300–RORC–IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4−/− gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4+ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.http://www.sciencedirect.com/science/article/pii/S2211383525003107IRF4IL-17APsoriasisPathogenesisCD4IL-23A |
| spellingShingle | Yanxia Yu Yirui Wang Weiwei Chen Chang Zhang Zhuo li Jing Yu Minhao Wang Can Song Sihao Yan Jiayi Lu Liangdan Sun Antisense oligonucleotides targeting IRF4 alleviate psoriasis Acta Pharmaceutica Sinica B IRF4 IL-17A Psoriasis Pathogenesis CD4 IL-23A |
| title | Antisense oligonucleotides targeting IRF4 alleviate psoriasis |
| title_full | Antisense oligonucleotides targeting IRF4 alleviate psoriasis |
| title_fullStr | Antisense oligonucleotides targeting IRF4 alleviate psoriasis |
| title_full_unstemmed | Antisense oligonucleotides targeting IRF4 alleviate psoriasis |
| title_short | Antisense oligonucleotides targeting IRF4 alleviate psoriasis |
| title_sort | antisense oligonucleotides targeting irf4 alleviate psoriasis |
| topic | IRF4 IL-17A Psoriasis Pathogenesis CD4 IL-23A |
| url | http://www.sciencedirect.com/science/article/pii/S2211383525003107 |
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