Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseases
Adaptor proteins are involved in various immune responses via the modulation of many signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that contains typical domains such as the pleckstrin homology (PH) domain, Src homology domain, and a proline-rich region from...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Open Exploration Publishing Inc.
2023-12-01
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| Series: | Exploration of Immunology |
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| Online Access: | https://www.explorationpub.com/Journals/ei/Article/1003125 |
| _version_ | 1797373061207425024 |
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| author | Yuto Sasaki Shoya Kawahara Yuichi Sekine Jun-Ichi Kashiwakura Kenji Oritani Tadashi Matsuda |
| author_facet | Yuto Sasaki Shoya Kawahara Yuichi Sekine Jun-Ichi Kashiwakura Kenji Oritani Tadashi Matsuda |
| author_sort | Yuto Sasaki |
| collection | DOAJ |
| description | Adaptor proteins are involved in various immune responses via the modulation of many signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that contains typical domains such as the pleckstrin homology (PH) domain, Src homology domain, and a proline-rich region from the N-terminal region. In T cells, STAP-2 positively regulates T cell receptor (TCR)-mediated signaling by associating with CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) and lymphocyte-specific protein tyrosine kinase (LCK). Therefore, a peptide that inhibits the interaction between STAP-2 and CD3ζ ITAMs is likely to suppress TCR-mediated T cell activation, as well as T cell-mediated diseases. As expected, the peptide successfully inhibited the STAP-2/CD3ζ ITAM interaction and suppressed TCR-mediated signaling, cell proliferation, and interleukin (IL)-2 production in human/murine T cells. Furthermore, this inhibitor suppressed the pathogenesis of experimental autoimmune encephalomyelitis (EAE), which is widely recognized as a mouse model of multiple sclerosis, via the downregulation of T cell activation and infiltration of T helper (Th) 1/Th17 cells. These results suggest a new strategy for the treatment of multiple sclerosis and other immune diseases. |
| first_indexed | 2024-03-08T18:43:50Z |
| format | Article |
| id | doaj.art-439caa0b65ef491788b1062cff2a7f16 |
| institution | Directory Open Access Journal |
| issn | 2768-6655 |
| language | English |
| last_indexed | 2024-03-08T18:43:50Z |
| publishDate | 2023-12-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Immunology |
| spelling | doaj.art-439caa0b65ef491788b1062cff2a7f162023-12-29T01:12:05ZengOpen Exploration Publishing Inc.Exploration of Immunology2768-66552023-12-013660461210.37349/ei.2023.00125Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseasesYuto Sasaki0https://orcid.org/0000-0002-3243-9777Shoya Kawahara1https://orcid.org/0009-0007-9985-0898Yuichi Sekine2https://orcid.org/0000-0002-2861-603XJun-Ichi Kashiwakura3https://orcid.org/0000-0002-7863-6696Kenji Oritani4https://orcid.org/0000-0002-5571-2457Tadashi Matsuda5https://orcid.org/0000-0002-3089-3757Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, JapanDepartment of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, JapanDepartment of Cell Biology, Kyoto Pharmaceutical University, Kyoto 607-8412, JapanDepartment of Life Science, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo 006-8585, JapanDepartment of Hematology, International University of Health and Welfare, Narita 286-8686, JapanDepartment of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, JapanAdaptor proteins are involved in various immune responses via the modulation of many signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that contains typical domains such as the pleckstrin homology (PH) domain, Src homology domain, and a proline-rich region from the N-terminal region. In T cells, STAP-2 positively regulates T cell receptor (TCR)-mediated signaling by associating with CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) and lymphocyte-specific protein tyrosine kinase (LCK). Therefore, a peptide that inhibits the interaction between STAP-2 and CD3ζ ITAMs is likely to suppress TCR-mediated T cell activation, as well as T cell-mediated diseases. As expected, the peptide successfully inhibited the STAP-2/CD3ζ ITAM interaction and suppressed TCR-mediated signaling, cell proliferation, and interleukin (IL)-2 production in human/murine T cells. Furthermore, this inhibitor suppressed the pathogenesis of experimental autoimmune encephalomyelitis (EAE), which is widely recognized as a mouse model of multiple sclerosis, via the downregulation of T cell activation and infiltration of T helper (Th) 1/Th17 cells. These results suggest a new strategy for the treatment of multiple sclerosis and other immune diseases.https://www.explorationpub.com/Journals/ei/Article/1003125signal-transducing adaptor proteinadaptor proteinsignal transductiont cell receptorimmune responseautoimmunitymultiple sclerosispeptides |
| spellingShingle | Yuto Sasaki Shoya Kawahara Yuichi Sekine Jun-Ichi Kashiwakura Kenji Oritani Tadashi Matsuda Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseases Exploration of Immunology signal-transducing adaptor protein adaptor protein signal transduction t cell receptor immune response autoimmunity multiple sclerosis peptides |
| title | Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseases |
| title_full | Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseases |
| title_fullStr | Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseases |
| title_full_unstemmed | Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseases |
| title_short | Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseases |
| title_sort | potential therapeutic applications of targeting signal transducing adaptor protein 2 in autoimmune diseases |
| topic | signal-transducing adaptor protein adaptor protein signal transduction t cell receptor immune response autoimmunity multiple sclerosis peptides |
| url | https://www.explorationpub.com/Journals/ei/Article/1003125 |
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