Targeting Th17 Cells with Small Molecules and Small Interference RNA
T helper 17 (Th17) cells play a central role in inflammatory and autoimmune diseases via the production of proinflammatory cytokines interleukin- (IL-) 17, IL-17F, and IL-22. Anti-IL-17 monoclonal antibodies show potent efficacy in psoriasis but poor effect in rheumatoid arthritis (RA) and Crohn’s d...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/290657 |
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| _version_ | 1849410881792770048 |
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| author | Hui Lin Pingfang Song Yi Zhao Li-Jia Xue Yi Liu Cong-Qiu Chu |
| author_facet | Hui Lin Pingfang Song Yi Zhao Li-Jia Xue Yi Liu Cong-Qiu Chu |
| author_sort | Hui Lin |
| collection | DOAJ |
| description | T helper 17 (Th17) cells play a central role in inflammatory and autoimmune diseases via the production of proinflammatory cytokines interleukin- (IL-) 17, IL-17F, and IL-22. Anti-IL-17 monoclonal antibodies show potent efficacy in psoriasis but poor effect in rheumatoid arthritis (RA) and Crohn’s disease. Alternative agents targeting Th17 cells may be a better way to inhibit the development and function of Th17 cells than antibodies of blocking a single effector cytokine. Retinoic acid-related orphan receptor gamma t (RORγt) which acts as the master transcription factor of Th17 differentiation has been an attractive pharmacologic target for the treatment of Th17-mediated autoimmune disease. Recent progress in technology of chemical screen and engineering nucleic acid enable two new classes of therapeutics targeting RORγt. Chemical screen technology identified several small molecule specific inhibitors of RORγt from a small molecule library. Systematic evolution of ligands by exponential enrichment (SELEX) technology enabled target specific aptamers to be isolated from a random sequence oligonucleotide library. In this review, we highlight the development and therapeutic potential of small molecules inhibiting Th17 cells by targeting RORγt and aptamer mediated CD4+ T cell specific delivery of small interference RNA against RORγt gene expression to inhibit pathogenic effector functions of Th17 lineage. |
| format | Article |
| id | doaj-art-60d0212236cb4e17bf8762481bd377e5 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-60d0212236cb4e17bf8762481bd377e52025-08-20T03:34:57ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/290657290657Targeting Th17 Cells with Small Molecules and Small Interference RNAHui Lin0Pingfang Song1Yi Zhao2Li-Jia Xue3Yi Liu4Cong-Qiu Chu5Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaDivision of Arthritis and Rheumatic Diseases, Oregon Health & Science University and VA Portland Health Care System, Portland, OR 97239, USADepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaDivision of Arthritis and Rheumatic Diseases, Oregon Health & Science University and VA Portland Health Care System, Portland, OR 97239, USAT helper 17 (Th17) cells play a central role in inflammatory and autoimmune diseases via the production of proinflammatory cytokines interleukin- (IL-) 17, IL-17F, and IL-22. Anti-IL-17 monoclonal antibodies show potent efficacy in psoriasis but poor effect in rheumatoid arthritis (RA) and Crohn’s disease. Alternative agents targeting Th17 cells may be a better way to inhibit the development and function of Th17 cells than antibodies of blocking a single effector cytokine. Retinoic acid-related orphan receptor gamma t (RORγt) which acts as the master transcription factor of Th17 differentiation has been an attractive pharmacologic target for the treatment of Th17-mediated autoimmune disease. Recent progress in technology of chemical screen and engineering nucleic acid enable two new classes of therapeutics targeting RORγt. Chemical screen technology identified several small molecule specific inhibitors of RORγt from a small molecule library. Systematic evolution of ligands by exponential enrichment (SELEX) technology enabled target specific aptamers to be isolated from a random sequence oligonucleotide library. In this review, we highlight the development and therapeutic potential of small molecules inhibiting Th17 cells by targeting RORγt and aptamer mediated CD4+ T cell specific delivery of small interference RNA against RORγt gene expression to inhibit pathogenic effector functions of Th17 lineage.http://dx.doi.org/10.1155/2015/290657 |
| spellingShingle | Hui Lin Pingfang Song Yi Zhao Li-Jia Xue Yi Liu Cong-Qiu Chu Targeting Th17 Cells with Small Molecules and Small Interference RNA Mediators of Inflammation |
| title | Targeting Th17 Cells with Small Molecules and Small Interference RNA |
| title_full | Targeting Th17 Cells with Small Molecules and Small Interference RNA |
| title_fullStr | Targeting Th17 Cells with Small Molecules and Small Interference RNA |
| title_full_unstemmed | Targeting Th17 Cells with Small Molecules and Small Interference RNA |
| title_short | Targeting Th17 Cells with Small Molecules and Small Interference RNA |
| title_sort | targeting th17 cells with small molecules and small interference rna |
| url | http://dx.doi.org/10.1155/2015/290657 |
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