TACI constrains TH17 pathogenicity and protects against gut inflammation
TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) plays critical roles in B cells by promoting immunoglobulin class switching and plasma cell survival. However, its expression and function in T cells remain controversial. We show here that TACI expression can be...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/145608 |
| _version_ | 1826127420528263168 |
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| author | Tan, Andy Hee-Meng Tso, Gloria Hoi Wan Zhang, Biyan Teo, Pei-Yun Ou, Xijun Ng, Sze-Wai Wong, Alex Xing Fah Tan, Sean Jing Xiang Sanny, Arleen Kim, Susana Soo-Yeon Lee, Alison P. Xu, Shengli Lam, Kong-Peng |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Tan, Andy Hee-Meng Tso, Gloria Hoi Wan Zhang, Biyan Teo, Pei-Yun Ou, Xijun Ng, Sze-Wai Wong, Alex Xing Fah Tan, Sean Jing Xiang Sanny, Arleen Kim, Susana Soo-Yeon Lee, Alison P. Xu, Shengli Lam, Kong-Peng |
| author_sort | Tan, Andy Hee-Meng |
| collection | NTU |
| description | TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) plays critical roles in B cells by promoting immunoglobulin class switching and plasma cell survival. However, its expression and function in T cells remain controversial. We show here that TACI expression can be strongly induced in murine CD4+ T cells in vitro by cytokines responsible for TH17 but not TH1 or TH2 differentiation. Frequencies and numbers of TH17 cells were elevated in TACI−/− compared with wild-type mice as well as among TACI−/− versus wild-type CD4+ T cells in mixed bone marrow chimeras, arguing for a T cell-intrinsic effect in the contribution of TACI deficiency to TH17 cell accumulation. TACI−/− mice were more susceptible to severe colitis induced by dextran sodium sulfate or adoptive T cell transfer, suggesting that TACI negatively regulates TH17 function and limits intestinal inflammation in a cell-autonomous manner. Finally, transcriptomic and biochemical analyses revealed that TACI−/− CD4+ T cells exhibited enhanced activation of TH17-promoting transcription factors NFAT, IRF4, c-MAF, and JUNB. Taken together, these findings reveal an important role of TACI in constraining TH17 pathogenicity and protecting against gut disease. |
| first_indexed | 2024-10-01T07:08:36Z |
| format | Journal Article |
| id | ntu-10356/145608 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:08:36Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1456082023-02-28T17:08:12Z TACI constrains TH17 pathogenicity and protects against gut inflammation Tan, Andy Hee-Meng Tso, Gloria Hoi Wan Zhang, Biyan Teo, Pei-Yun Ou, Xijun Ng, Sze-Wai Wong, Alex Xing Fah Tan, Sean Jing Xiang Sanny, Arleen Kim, Susana Soo-Yeon Lee, Alison P. Xu, Shengli Lam, Kong-Peng School of Biological Sciences Bioprocessing Technology Institute, A*STAR Singapore Immunology Network, A*STAR Science::Biological sciences Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor Immunoglobulin TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) plays critical roles in B cells by promoting immunoglobulin class switching and plasma cell survival. However, its expression and function in T cells remain controversial. We show here that TACI expression can be strongly induced in murine CD4+ T cells in vitro by cytokines responsible for TH17 but not TH1 or TH2 differentiation. Frequencies and numbers of TH17 cells were elevated in TACI−/− compared with wild-type mice as well as among TACI−/− versus wild-type CD4+ T cells in mixed bone marrow chimeras, arguing for a T cell-intrinsic effect in the contribution of TACI deficiency to TH17 cell accumulation. TACI−/− mice were more susceptible to severe colitis induced by dextran sodium sulfate or adoptive T cell transfer, suggesting that TACI negatively regulates TH17 function and limits intestinal inflammation in a cell-autonomous manner. Finally, transcriptomic and biochemical analyses revealed that TACI−/− CD4+ T cells exhibited enhanced activation of TH17-promoting transcription factors NFAT, IRF4, c-MAF, and JUNB. Taken together, these findings reveal an important role of TACI in constraining TH17 pathogenicity and protecting against gut disease. Agency for Science, Technology and Research (A*STAR) Published version We thank staff of the Biological Resource Centre (BRC) for care and maintenance of mice and members of the laboratory for insightful discussions. The Advanced Molecular Pathology Laboratory (AMPL) of the Institute of Molecular and Cell Biology assisted in the preparation and histological staining of colon samples. This research was supported by Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore (A∗STAR). 2020-12-30T02:56:54Z 2020-12-30T02:56:54Z 2020 Journal Article Tan, A. H.-M., Tso, G. H. W., Zhang, B., Teo, P.-Y., Ou, X., Ng, S.-W., . . . Lam, K.-P. (2020). TACI constrains TH17 pathogenicity and protects against gut inflammation. iScience, 23(11), 101707-. doi:10.1016/j.isci.2020.101707 2589-0042 https://hdl.handle.net/10356/145608 10.1016/j.isci.2020.101707 33205021 11 23 en iScience © 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf |
| spellingShingle | Science::Biological sciences Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor Immunoglobulin Tan, Andy Hee-Meng Tso, Gloria Hoi Wan Zhang, Biyan Teo, Pei-Yun Ou, Xijun Ng, Sze-Wai Wong, Alex Xing Fah Tan, Sean Jing Xiang Sanny, Arleen Kim, Susana Soo-Yeon Lee, Alison P. Xu, Shengli Lam, Kong-Peng TACI constrains TH17 pathogenicity and protects against gut inflammation |
| title | TACI constrains TH17 pathogenicity and protects against gut inflammation |
| title_full | TACI constrains TH17 pathogenicity and protects against gut inflammation |
| title_fullStr | TACI constrains TH17 pathogenicity and protects against gut inflammation |
| title_full_unstemmed | TACI constrains TH17 pathogenicity and protects against gut inflammation |
| title_short | TACI constrains TH17 pathogenicity and protects against gut inflammation |
| title_sort | taci constrains th17 pathogenicity and protects against gut inflammation |
| topic | Science::Biological sciences Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor Immunoglobulin |
| url | https://hdl.handle.net/10356/145608 |
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