Back to Search
Start Over
IL-12 drives the differentiation of human T follicular regulatory cells.
- Source :
- Science Immunology; Jul2024, Vol. 9 Issue 97, p1-17, 17p
- Publication Year :
- 2024
-
Abstract
- T follicular regulatory (T<subscript>fr</subscript>) cells can counteract the B cell helper activity of T follicular helper (T<subscript>fh</subscript>) 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 (T<subscript>reg</subscript>) cells into T<subscript>fr</subscript> cells is still missing. Herein, we report that low doses of the pro-T<subscript>fh</subscript> cytokine interleukin-12 (IL-12) drive the induction of a T<subscript>fr</subscript> cell program on activated human T<subscript>reg</subscript> 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 T<subscript>fr</subscript> cells and produced higher levels of anti-actin autoantibodies in vivo. Overall, this study unveils IL-12 as an inducer of T<subscript>fr</subscript> cell differentiation in vivo and provides an approach for the in vitro generation of human T<subscript>fr</subscript>-like cells. Editor's summary: T follicular regulatory (T<subscript>fr</subscript>) cells balance the activity of T follicular helper cells and suppress B cell responses to self-antigens and allergens. However, the key signals involved in T<subscript>fr</subscript> cell differentiation, particularly in humans, remain incompletely understood. By screening the effects of multiple cytokines on human regulatory T cells, Castaño et al. identified interleukin-12 (IL-12) as the most potent inducer of T<subscript>fr</subscript> cell differentiation in vitro. IL-12 promoted the acquisition of a follicular gene expression program and STAT4 (signal transducer and activator of transcription 4) binding at signature follicular loci. In addition, patients bearing mutations in the IL12RB1 gene displayed a strong decrease in circulating T<subscript>fr</subscript> cells. Together, these findings identify IL-12 as a driver of human T<subscript>fr</subscript> cell differentiation, thus enabling their in vitro generation. —Claire Olingy [ABSTRACT FROM AUTHOR]
- Subjects :
- T helper cells
REGULATORY T cells
B cells
CELL differentiation
GENETIC transcription
Subjects
Details
- Language :
- English
- ISSN :
- 24709468
- Volume :
- 9
- Issue :
- 97
- Database :
- Complementary Index
- Journal :
- Science Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 178817281
- Full Text :
- https://doi.org/10.1126/sciimmunol.adf2047