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 (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.

• 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/