IL-12 drives the differentiation of human T follicular regulatory cells
ABSTRACT: T follicular regulatory (Tfr) cells can counteract the B cell helper activity of T follicular helper (Tfh) cells and hinder the production of antibodies against self-antigens or allergens. A mechanistic understanding of the cytokines initiating the differentiation of human regulatory T (Tr...
- Autores:
-
Castaño Monsalve, Diana María
Rico Puerta, María Camila
Bonasio, Roberto
Bustamante, Jacinta
Casanova, Jean-Laurent
Feng, Allan
Garcia, Segovia Atencio
Henrickson, Sarah
Le Coz, Carole
Locci, Michela
Romberg, Neil
Shields, Emily
Sharpe, Hannah
Tobias, John W
Utz, Paul
Wang, Sidney
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2024
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/43140
- Acceso en línea:
- https://hdl.handle.net/10495/43140
- Palabra clave:
- Diferenciación Celular - immunología
Cell Differentiation - immunology
Interleucina-12 - immunología
Interleukin-12 - immunology
Receptores de Interleucina-12
Receptors, Interleukin-12
Factor de Transcripción STAT4
STAT4 Transcription Factor
Linfocitos T Reguladores - immunología
T-Lymphocytes, Regulatory - immunology
https://id.nlm.nih.gov/mesh/D053707
https://id.nlm.nih.gov/mesh/D002454
https://id.nlm.nih.gov/mesh/D018664
https://id.nlm.nih.gov/mesh/D050797
https://id.nlm.nih.gov/mesh/D050378
- Rights
- openAccess
- License
- https://creativecommons.org/licenses/by/4.0/
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|
| dc.title.spa.fl_str_mv |
IL-12 drives the differentiation of human T follicular regulatory cells |
| title |
IL-12 drives the differentiation of human T follicular regulatory cells |
| spellingShingle |
IL-12 drives the differentiation of human T follicular regulatory cells Diferenciación Celular - immunología Cell Differentiation - immunology Interleucina-12 - immunología Interleukin-12 - immunology Receptores de Interleucina-12 Receptors, Interleukin-12 Factor de Transcripción STAT4 STAT4 Transcription Factor Linfocitos T Reguladores - immunología T-Lymphocytes, Regulatory - immunology https://id.nlm.nih.gov/mesh/D053707 https://id.nlm.nih.gov/mesh/D002454 https://id.nlm.nih.gov/mesh/D018664 https://id.nlm.nih.gov/mesh/D050797 https://id.nlm.nih.gov/mesh/D050378 |
| title_short |
IL-12 drives the differentiation of human T follicular regulatory cells |
| title_full |
IL-12 drives the differentiation of human T follicular regulatory cells |
| title_fullStr |
IL-12 drives the differentiation of human T follicular regulatory cells |
| title_full_unstemmed |
IL-12 drives the differentiation of human T follicular regulatory cells |
| title_sort |
IL-12 drives the differentiation of human T follicular regulatory cells |
| dc.creator.fl_str_mv |
Castaño Monsalve, Diana María Rico Puerta, María Camila Bonasio, Roberto Bustamante, Jacinta Casanova, Jean-Laurent Feng, Allan Garcia, Segovia Atencio Henrickson, Sarah Le Coz, Carole Locci, Michela Romberg, Neil Shields, Emily Sharpe, Hannah Tobias, John W Utz, Paul Wang, Sidney |
| dc.contributor.author.none.fl_str_mv |
Castaño Monsalve, Diana María Rico Puerta, María Camila Bonasio, Roberto Bustamante, Jacinta Casanova, Jean-Laurent Feng, Allan Garcia, Segovia Atencio Henrickson, Sarah Le Coz, Carole Locci, Michela Romberg, Neil Shields, Emily Sharpe, Hannah Tobias, John W Utz, Paul Wang, Sidney |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de Inmunología Celular e Inmunogenética |
| dc.subject.decs.none.fl_str_mv |
Diferenciación Celular - immunología Cell Differentiation - immunology Interleucina-12 - immunología Interleukin-12 - immunology Receptores de Interleucina-12 Receptors, Interleukin-12 Factor de Transcripción STAT4 STAT4 Transcription Factor Linfocitos T Reguladores - immunología T-Lymphocytes, Regulatory - immunology |
| topic |
Diferenciación Celular - immunología Cell Differentiation - immunology Interleucina-12 - immunología Interleukin-12 - immunology Receptores de Interleucina-12 Receptors, Interleukin-12 Factor de Transcripción STAT4 STAT4 Transcription Factor Linfocitos T Reguladores - immunología T-Lymphocytes, Regulatory - immunology https://id.nlm.nih.gov/mesh/D053707 https://id.nlm.nih.gov/mesh/D002454 https://id.nlm.nih.gov/mesh/D018664 https://id.nlm.nih.gov/mesh/D050797 https://id.nlm.nih.gov/mesh/D050378 |
| dc.subject.agrovoc.none.fl_str_mv |
https://id.nlm.nih.gov/mesh/D053707 |
| dc.subject.meshuri.none.fl_str_mv |
https://id.nlm.nih.gov/mesh/D002454 https://id.nlm.nih.gov/mesh/D018664 https://id.nlm.nih.gov/mesh/D050797 https://id.nlm.nih.gov/mesh/D050378 |
| description |
ABSTRACT: T follicular regulatory (Tfr) cells can counteract the B cell helper activity of T follicular helper (Tfh) cells and hinder the production of antibodies against self-antigens or allergens. A mechanistic understanding of the cytokines initiating the differentiation of human regulatory T (Treg) cells into Tfr cells is still missing. Herein, we report that low doses of the pro-Tfh cytokine interleukin-12 (IL-12) drive the induction of a Tfr cell program on activated human Treg cells while also preserving their regulatory function. Mechanistically, we found that IL-12 led to STAT4 (signal transducer and activator of transcription 4) phosphorylation and binding to IL-12-driven follicular signature genes. Patients with inborn errors of immunity in the IL12RB1 gene presented with a strong decrease in circulating Tfr cells and produced higher levels of anti-actin autoantibodies in vivo. Overall, this study unveils IL-12 as an inducer of Tfr cell differentiation in vivo and provides an approach for the in vitro generation of human Tfr-like cells. |
| publishDate |
2024 |
| dc.date.accessioned.none.fl_str_mv |
2024-11-04T19:02:55Z |
| dc.date.available.none.fl_str_mv |
2024-11-04T19:02:55Z |
| dc.date.issued.none.fl_str_mv |
2024 |
| dc.type.spa.fl_str_mv |
Artículo de investigación |
| dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
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https://purl.org/redcol/resource_type/ART |
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http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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publishedVersion |
| dc.identifier.citation.spa.fl_str_mv |
Castaño D, Wang S, Atencio-Garcia S, Shields EJ, Rico MC, Sharpe H, Bustamante J, Feng A, Le Coz C, Romberg N, Tobias JW, Utz PJ, Henrickson SE, Casanova JL, Bonasio R, Locci M. IL-12 drives the differentiation of human T follicular regulatory cells. Sci Immunol. 2024 Jul 5;9(97):eadf2047. doi: 10.1126/sciimmunol.adf2047 |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/10495/43140 |
| dc.identifier.doi.none.fl_str_mv |
10.1126/sciimmunol.adf2047. |
| dc.identifier.eissn.none.fl_str_mv |
2470-9468 |
| identifier_str_mv |
Castaño D, Wang S, Atencio-Garcia S, Shields EJ, Rico MC, Sharpe H, Bustamante J, Feng A, Le Coz C, Romberg N, Tobias JW, Utz PJ, Henrickson SE, Casanova JL, Bonasio R, Locci M. IL-12 drives the differentiation of human T follicular regulatory cells. Sci Immunol. 2024 Jul 5;9(97):eadf2047. doi: 10.1126/sciimmunol.adf2047 10.1126/sciimmunol.adf2047. 2470-9468 |
| url |
https://hdl.handle.net/10495/43140 |
| dc.language.iso.spa.fl_str_mv |
eng |
| language |
eng |
| dc.relation.ispartofjournalabbrev.spa.fl_str_mv |
Sci. Immunol. |
| dc.relation.citationendpage.spa.fl_str_mv |
17 |
| dc.relation.citationissue.spa.fl_str_mv |
97 |
| dc.relation.citationstartpage.spa.fl_str_mv |
1 |
| dc.relation.citationvolume.spa.fl_str_mv |
9 |
| dc.relation.ispartofjournal.spa.fl_str_mv |
Science immunology |
| dc.rights.uri.spa.fl_str_mv |
https://creativecommons.org/licenses/by/4.0/ |
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http://creativecommons.org/licenses/by/2.5/co/ |
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info:eu-repo/semantics/openAccess |
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openAccess |
| dc.format.extent.spa.fl_str_mv |
17 páginas |
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application/pdf |
| dc.publisher.spa.fl_str_mv |
American Association for the Advancement of Science |
| dc.publisher.place.spa.fl_str_mv |
Washington, Estados Unidos |
| institution |
Universidad de Antioquia |
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Castaño Monsalve, Diana MaríaRico Puerta, María CamilaBonasio, RobertoBustamante, JacintaCasanova, Jean-LaurentFeng, AllanGarcia, Segovia AtencioHenrickson, SarahLe Coz, CaroleLocci, MichelaRomberg, NeilShields, EmilySharpe, HannahTobias, John WUtz, PaulWang, SidneyGrupo de Inmunología Celular e Inmunogenética2024-11-04T19:02:55Z2024-11-04T19:02:55Z2024Castaño D, Wang S, Atencio-Garcia S, Shields EJ, Rico MC, Sharpe H, Bustamante J, Feng A, Le Coz C, Romberg N, Tobias JW, Utz PJ, Henrickson SE, Casanova JL, Bonasio R, Locci M. IL-12 drives the differentiation of human T follicular regulatory cells. Sci Immunol. 2024 Jul 5;9(97):eadf2047. doi: 10.1126/sciimmunol.adf2047https://hdl.handle.net/10495/4314010.1126/sciimmunol.adf2047.2470-9468ABSTRACT: T follicular regulatory (Tfr) cells can counteract the B cell helper activity of T follicular helper (Tfh) cells and hinder the production of antibodies against self-antigens or allergens. A mechanistic understanding of the cytokines initiating the differentiation of human regulatory T (Treg) cells into Tfr cells is still missing. Herein, we report that low doses of the pro-Tfh cytokine interleukin-12 (IL-12) drive the induction of a Tfr cell program on activated human Treg cells while also preserving their regulatory function. Mechanistically, we found that IL-12 led to STAT4 (signal transducer and activator of transcription 4) phosphorylation and binding to IL-12-driven follicular signature genes. Patients with inborn errors of immunity in the IL12RB1 gene presented with a strong decrease in circulating Tfr cells and produced higher levels of anti-actin autoantibodies in vivo. Overall, this study unveils IL-12 as an inducer of Tfr cell differentiation in vivo and provides an approach for the in vitro generation of human Tfr-like cells.National Institutes of HealthCOL000863917 páginasapplication/pdfengAmerican Association for the Advancement of ScienceWashington, Estados Unidoshttps://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/2.5/co/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2IL-12 drives the differentiation of human T follicular regulatory cellsArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionDiferenciación Celular - immunologíaCell Differentiation - immunologyInterleucina-12 - immunologíaInterleukin-12 - immunologyReceptores de Interleucina-12Receptors, Interleukin-12Factor de Transcripción STAT4STAT4 Transcription FactorLinfocitos T Reguladores - immunologíaT-Lymphocytes, Regulatory - immunologyhttps://id.nlm.nih.gov/mesh/D053707https://id.nlm.nih.gov/mesh/D002454https://id.nlm.nih.gov/mesh/D018664https://id.nlm.nih.gov/mesh/D050797https://id.nlm.nih.gov/mesh/D050378Sci. 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