FoxA1 Directs the Lineage and Immunosuppressive Properties of a Novel Regulatory T Cell Population in EAE and MS
Overview
Molecular Biology
Authors
Affiliations
The defective generation or function of regulatory T (Treg) cells in autoimmune disease contributes to chronic inflammation and tissue injury. We report the identification of FoxA1 as a transcription factor in T cells that, after ectopic expression, confers suppressive properties in a newly identified Treg cell population, herein called FoxA1(+) Treg cells. FoxA1 bound to the Pdl1 promoter, inducing programmed cell death ligand 1 (Pd-l1) expression, which was essential for the FoxA1(+) Treg cells to kill activated T cells. FoxA1(+) Treg cells develop primarily in the central nervous system in response to autoimmune inflammation, have a distinct transcriptional profile and are CD4(+)FoxA1(+)CD47(+)CD69(+)PD-L1(hi)FoxP3(-). Adoptive transfer of stable FoxA1(+) Treg cells inhibited experimental autoimmune encephalomyelitis in a FoxA1-and Pd-l1-dependent manner. The development of FoxA1(+) Treg cells is induced by interferon-β (IFN-β) and requires T cell-intrinsic IFN-α/β receptor (Ifnar) signaling, as the frequency of FoxA1(+) Treg cells was reduced in Ifnb(-/-) and Ifnar(-/-) mice. In individuals with relapsing-remitting multiple sclerosis, clinical response to treatment with IFN-β was associated with an increased frequency of suppressive FoxA1(+) Treg cells in the blood. These findings suggest that FoxA1 is a lineage-specification factor that is induced by IFN-β and supports the differentiation and suppressive function of FoxA1(+) Treg cells.
Yang G, Tian L, Wang Y Discov Oncol. 2025; 16(1):12.
PMID: 39760792 PMC: 11703795. DOI: 10.1007/s12672-025-01749-3.
Neurons upregulate PD-L1 via IFN/STAT1/IRF1 to alleviate damage by CD8 T cells in cerebral malaria.
Wang Y, Shen Y, Liang J, Wang S, Huang Y, Zhu Q J Neuroinflammation. 2024; 21(1):119.
PMID: 38715061 PMC: 11077882. DOI: 10.1186/s12974-024-03114-7.
Leichtle A, Jeschke S, Plotze-Martin K, Idel C, Bruchhage K, Pries R J Pers Med. 2024; 14(3).
PMID: 38541021 PMC: 10971202. DOI: 10.3390/jpm14030279.
Berberine: A natural modulator of immune cells in multiple sclerosis.
Yazdanpanah E, Dadfar S, Shadab A, Orooji N, Nemati M, Pazoki A Immun Inflamm Dis. 2024; 12(3):e1213.
PMID: 38477663 PMC: 10936236. DOI: 10.1002/iid3.1213.
Mandatori S, Liu Y, Marturia-Navarro J, Hadi M, Henriksen K, Zheng J Sci Adv. 2023; 9(51):eadj8442.
PMID: 38117896 PMC: 10732530. DOI: 10.1126/sciadv.adj8442.