Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway
Calcineurin (Cn) is a protein phosphatase that regulates the activation of the nuclear factor of activated T-cells (NFAT) family of transcription factors, which are key regulators of T-cell development and function. Here, we generated a conditional Cnb1 mouse model in which Cnb1 was specifically del...
| Principais autores: | , , , , , , , |
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| Formato: | Journal Article |
| Idioma: | English |
| Publicado em: |
2018
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| Acesso em linha: | https://hdl.handle.net/10356/87680 http://hdl.handle.net/10220/45534 |
| _version_ | 1826124834211364864 |
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| author | Mencarelli, Andrea Vacca, Maurizio Khameneh, Hanif Javanmard Acerbi, Enzo Tay, Alicia Zolezzi, Francesca Poidinger, Michael Mortellaro, Alessandra |
| author2 | Singapore Centre for Environmental Life Sciences Engineering |
| author_facet | Singapore Centre for Environmental Life Sciences Engineering Mencarelli, Andrea Vacca, Maurizio Khameneh, Hanif Javanmard Acerbi, Enzo Tay, Alicia Zolezzi, Francesca Poidinger, Michael Mortellaro, Alessandra |
| author_sort | Mencarelli, Andrea |
| collection | NTU |
| description | Calcineurin (Cn) is a protein phosphatase that regulates the activation of the nuclear factor of activated T-cells (NFAT) family of transcription factors, which are key regulators of T-cell development and function. Here, we generated a conditional Cnb1 mouse model in which Cnb1 was specifically deleted in CD4+ T cells (Cnb1CD4 mice) to delineate the role of the Cn–NFAT pathway in immune homeostasis of the intestine. The Cnb1CD4 mice developed severe, spontaneous colitis characterized at the molecular level by an increased T helper-1-cell response but an unaltered regulatory T-cell compartment. Antibiotic treatment ameliorated the intestinal inflammation observed in Cnb1CD4 mice, suggesting that the microbiota contributes to the onset of colitis. CD4+ T cells isolated from Cnb1CD4 mice produced high levels of IFNγ due to increased activation of the JAK2/STAT4 pathway induced by IL-12. Our data highlight that Cn signaling in CD4+ T cells is critical for intestinal immune homeostasis in part by inhibiting IL-12 responsiveness of CD4+ T cells. |
| first_indexed | 2024-10-01T06:26:50Z |
| format | Journal Article |
| id | ntu-10356/87680 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:26:50Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/876802020-09-21T11:34:42Z Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway Mencarelli, Andrea Vacca, Maurizio Khameneh, Hanif Javanmard Acerbi, Enzo Tay, Alicia Zolezzi, Francesca Poidinger, Michael Mortellaro, Alessandra Singapore Centre for Environmental Life Sciences Engineering Calcineurin B Nuclear Factor of Activated T Cell Calcineurin (Cn) is a protein phosphatase that regulates the activation of the nuclear factor of activated T-cells (NFAT) family of transcription factors, which are key regulators of T-cell development and function. Here, we generated a conditional Cnb1 mouse model in which Cnb1 was specifically deleted in CD4+ T cells (Cnb1CD4 mice) to delineate the role of the Cn–NFAT pathway in immune homeostasis of the intestine. The Cnb1CD4 mice developed severe, spontaneous colitis characterized at the molecular level by an increased T helper-1-cell response but an unaltered regulatory T-cell compartment. Antibiotic treatment ameliorated the intestinal inflammation observed in Cnb1CD4 mice, suggesting that the microbiota contributes to the onset of colitis. CD4+ T cells isolated from Cnb1CD4 mice produced high levels of IFNγ due to increased activation of the JAK2/STAT4 pathway induced by IL-12. Our data highlight that Cn signaling in CD4+ T cells is critical for intestinal immune homeostasis in part by inhibiting IL-12 responsiveness of CD4+ T cells. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2018-08-08T01:56:11Z 2019-12-06T16:47:08Z 2018-08-08T01:56:11Z 2019-12-06T16:47:08Z 2018 Journal Article Mencarelli, A., Vacca, M., Khameneh, H. J., Acerbi, E., Tay, A., Zolezzi, F., et al. (2018). Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway. Frontiers in Immunology, 9, 261-. https://hdl.handle.net/10356/87680 http://hdl.handle.net/10220/45534 10.3389/fimmu.2018.00261 en Frontiers in Immunology © 2018 Mencarelli, Vacca, Khameneh, Acerbi, Tay, Zolezzi, Poidinger and Mortellaro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. 15 p. application/pdf |
| spellingShingle | Calcineurin B Nuclear Factor of Activated T Cell Mencarelli, Andrea Vacca, Maurizio Khameneh, Hanif Javanmard Acerbi, Enzo Tay, Alicia Zolezzi, Francesca Poidinger, Michael Mortellaro, Alessandra Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway |
| title | Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway |
| title_full | Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway |
| title_fullStr | Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway |
| title_full_unstemmed | Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway |
| title_short | Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway |
| title_sort | calcineurin b in cd4 t cells prevents autoimmune colitis by negatively regulating the jak stat pathway |
| topic | Calcineurin B Nuclear Factor of Activated T Cell |
| url | https://hdl.handle.net/10356/87680 http://hdl.handle.net/10220/45534 |
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