T Follicular Regulatory Cell–Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity
© 2020 by The American Association of Immunologists, Inc. T follicular regulatory (TFR) cells limit Ab responses, but the underlying mechanisms remain largely unknown. In this study, we identify Fgl2 as a soluble TFR cell effector molecule through single-cell gene expression profiling. Highly expres...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The American Association of Immunologists
2021
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| Online Access: | https://hdl.handle.net/1721.1/138496 |
| _version_ | 1826201444961746944 |
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| author | Sungnak, Waradon Wagner, Allon Kowalczyk, Monika S Bod, Lloyd Kye, Yoon-Chul Sage, Peter T Sharpe, Arlene H Sobel, Raymond A Quintana, Francisco J Rozenblatt-Rosen, Orit Regev, Aviv Wang, Chao Yosef, Nir Kuchroo, Vijay K |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Sungnak, Waradon Wagner, Allon Kowalczyk, Monika S Bod, Lloyd Kye, Yoon-Chul Sage, Peter T Sharpe, Arlene H Sobel, Raymond A Quintana, Francisco J Rozenblatt-Rosen, Orit Regev, Aviv Wang, Chao Yosef, Nir Kuchroo, Vijay K |
| author_sort | Sungnak, Waradon |
| collection | MIT |
| description | © 2020 by The American Association of Immunologists, Inc. T follicular regulatory (TFR) cells limit Ab responses, but the underlying mechanisms remain largely unknown. In this study, we identify Fgl2 as a soluble TFR cell effector molecule through single-cell gene expression profiling. Highly expressed by TFR cells, Fgl2 directly binds to B cells, especially light-zone germinal center B cells, as well as to T follicular helper (TFH) cells, and directly regulates B cells and TFH in a context-dependent and type 2 Ab isotype-specific manner. In TFH cells, Fgl2 induces the expression of Prdm1 and a panel of checkpoint molecules, including PD1, TIM3, LAG3, and TIGIT, resulting in TFH cell dysfunction. Mice deficient in Fgl2 had dysregulated Ab responses at steady-state and upon immunization. In addition, loss of Fgl2 results in expansion of autoreactive B cells upon immunization. Consistent with this observation, aged Fgl2-/- mice spontaneously developed autoimmunity associated with elevated autoantibodies. Thus, Fgl2 is a TFR cell effector molecule that regulates humoral immunity and limits systemic autoimmunity. |
| first_indexed | 2024-09-23T11:51:39Z |
| format | Article |
| id | mit-1721.1/138496 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:51:39Z |
| publishDate | 2021 |
| publisher | The American Association of Immunologists |
| record_format | dspace |
| spelling | mit-1721.1/1384962023-08-11T17:45:57Z T Follicular Regulatory Cell–Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity Sungnak, Waradon Wagner, Allon Kowalczyk, Monika S Bod, Lloyd Kye, Yoon-Chul Sage, Peter T Sharpe, Arlene H Sobel, Raymond A Quintana, Francisco J Rozenblatt-Rosen, Orit Regev, Aviv Wang, Chao Yosef, Nir Kuchroo, Vijay K Massachusetts Institute of Technology. Department of Biology © 2020 by The American Association of Immunologists, Inc. T follicular regulatory (TFR) cells limit Ab responses, but the underlying mechanisms remain largely unknown. In this study, we identify Fgl2 as a soluble TFR cell effector molecule through single-cell gene expression profiling. Highly expressed by TFR cells, Fgl2 directly binds to B cells, especially light-zone germinal center B cells, as well as to T follicular helper (TFH) cells, and directly regulates B cells and TFH in a context-dependent and type 2 Ab isotype-specific manner. In TFH cells, Fgl2 induces the expression of Prdm1 and a panel of checkpoint molecules, including PD1, TIM3, LAG3, and TIGIT, resulting in TFH cell dysfunction. Mice deficient in Fgl2 had dysregulated Ab responses at steady-state and upon immunization. In addition, loss of Fgl2 results in expansion of autoreactive B cells upon immunization. Consistent with this observation, aged Fgl2-/- mice spontaneously developed autoimmunity associated with elevated autoantibodies. Thus, Fgl2 is a TFR cell effector molecule that regulates humoral immunity and limits systemic autoimmunity. 2021-12-16T13:57:02Z 2021-12-16T13:57:02Z 2020 2021-12-16T13:42:25Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/138496 Sungnak, Waradon, Wagner, Allon, Kowalczyk, Monika S, Bod, Lloyd, Kye, Yoon-Chul et al. 2020. "T Follicular Regulatory Cell–Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity." Journal of immunology, 205 (12). en 10.4049/JIMMUNOL.2000748 Journal of immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf The American Association of Immunologists PMC |
| spellingShingle | Sungnak, Waradon Wagner, Allon Kowalczyk, Monika S Bod, Lloyd Kye, Yoon-Chul Sage, Peter T Sharpe, Arlene H Sobel, Raymond A Quintana, Francisco J Rozenblatt-Rosen, Orit Regev, Aviv Wang, Chao Yosef, Nir Kuchroo, Vijay K T Follicular Regulatory Cell–Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity |
| title | T Follicular Regulatory Cell–Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity |
| title_full | T Follicular Regulatory Cell–Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity |
| title_fullStr | T Follicular Regulatory Cell–Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity |
| title_full_unstemmed | T Follicular Regulatory Cell–Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity |
| title_short | T Follicular Regulatory Cell–Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity |
| title_sort | t follicular regulatory cell derived fibrinogen like protein 2 regulates production of autoantibodies and induction of systemic autoimmunity |
| url | https://hdl.handle.net/1721.1/138496 |
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