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Therapeutic Advantage of Tyk2 Inhibition for Treating Autoimmune and Chronic Inflammatory Diseases
| Title: | Therapeutic Advantage of Tyk2 Inhibition for Treating Autoimmune and Chronic Inflammatory Diseases |
| Authors: | Muromoto, Ryuta Browse this author →KAKEN DB | | Shimoda, Kazuya Browse this author →KAKEN DB | | Oritani, Kenji Browse this author →KAKEN DB | | Matsuda, Tadashi Browse this author →KAKEN DB |
| Keywords: | tyrosine kinase 2 (Tyk2) | | cytokine | | signal transduction | | immune system | | Janus family of protein tyrosine kinase (Jak) inhibitor | | therapy |
| Issue Date: | 1-Nov-2021 |
| Publisher: | The Pharmaceutical Society of Japan |
| Journal Title: | Biological & pharmaceutical bulletin |
| Volume: | 44 |
| Issue: | 11 |
| Start Page: | 1585 |
| End Page: | 1592 |
| Publisher DOI: | 10.1248/bpb.b21-00609 |
| PMID: | 34719635 |
| Abstract: | Tyrosine kinase 2 (Tyk2) is a member of the Janus family of protein tyrosine kinases (Jaks). Tyk2 associates with interferon (IFN)-α, IFN-β, interleukin (IL)-6, IL-10, IL-12, and IL-23 receptors and mediates their downstream signaling pathways. Based on our data using Tyk2-deficient mice and cells, Tyk2 plays crucial roles in the differentiation, maintenance, and function of T helper 1 (Th1) and Th17 cells, and its dysregulation may promote autoimmune and/or inflammatory diseases. IFN-α-induced growth inhibition of B lymphocyte progenitors is dependent on Tyk2-mediated signals to regulate death-associated protein (Daxx) nuclear localization and Daxx-promyelocytic leukemia protein interactions. Tyk2-deficient mice show impaired constitutive production of type I IFNs by macrophages under steady-state conditions. When heat-killed Cutibacterium acnes is injected intraperitoneally, Tyk2-deficient mice show less granuloma formation through enhanced prostaglandin E2 and protein kinase A activities, leading to high IL-10 production by macrophages. Thus, Tyk2 is widely involved in the immune and inflammatory response at multiple events; therefore, Tyk2 is likely to be a suitable target for treating patients with autoimmune and/or chronic inflammatory diseases. Clinical trials of Tyk2 inhibitors have shown higher response rates and improved tolerability in the treatment of patients with psoriasis and inflammatory bowel diseases. Taken together, Tyk2 inhibition has great potential for clinical application in the management of a variety of diseases. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/87614 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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