Treg cell plasticity as a driver of inflammation in spondyloarthritis and psoriasis
Regulatory T cells (Tregs) are critical for maintaining immune tolerance by suppressing effector T cell responses. However, in chronic inflammatory diseases such as spondyloarthritis (SpA) and psoriasis (PsO), Tregs can lose their stability and acquire pro-inflammatory characteristics, a phenomenon...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621396/full |
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| author | Ingrid Itzayanna Ortega-Mejia Ingrid Itzayanna Ortega-Mejia Nayeli Romero-López Nayeli Romero-López Julio César Casasola-Vargas Rubén Burgos-Vargas María Lilia Domínguez-López José Pablo Romero-López |
| author_facet | Ingrid Itzayanna Ortega-Mejia Ingrid Itzayanna Ortega-Mejia Nayeli Romero-López Nayeli Romero-López Julio César Casasola-Vargas Rubén Burgos-Vargas María Lilia Domínguez-López José Pablo Romero-López |
| author_sort | Ingrid Itzayanna Ortega-Mejia |
| collection | DOAJ |
| description | Regulatory T cells (Tregs) are critical for maintaining immune tolerance by suppressing effector T cell responses. However, in chronic inflammatory diseases such as spondyloarthritis (SpA) and psoriasis (PsO), Tregs can lose their stability and acquire pro-inflammatory characteristics, a phenomenon known as Treg plasticity. Under inflammatory conditions, Tregs may downregulate FoxP3, upregulate RORγt, and produce cytokines such as IL-17 and IFN-γ, thus losing their suppressive function and contributing to disease progression. In SpA, altered numbers and impaired Treg function have been identified in peripheral blood and synovial fluid. Specific subsets, such as CD161+ Tregs with Th17-like features, suggest that inflammatory cytokines and signals like STAT3 activation and ICOS engagement promote pathogenic reprogramming. Genetic factors, including HLA-B27, may further predispose Tregs to instability. Single-cell transcriptomic analyses have provided evidence of shared TCR repertoires between Tregs and effector T cells, reinforcing the concept of lineage plasticity. Similarly, in PsO, skin-resident Tregs exposed to IL-23, IL-6, and IL-21 can acquire a Th17-like phenotype, producing IL-17A and exacerbating local inflammation. Environmental factors such as hypoxia also contribute to destabilizing Treg identity. The persistence of pathogenic Tregs, even following therapy blockade of IL-17 or IL-23, highlights the challenge of achieving long-term disease remission. |
| format | Article |
| id | doaj-art-12dc4e56fab4408fa75bbd7e52802756 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-12dc4e56fab4408fa75bbd7e528027562025-08-20T03:32:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16213961621396Treg cell plasticity as a driver of inflammation in spondyloarthritis and psoriasisIngrid Itzayanna Ortega-Mejia0Ingrid Itzayanna Ortega-Mejia1Nayeli Romero-López2Nayeli Romero-López3Julio César Casasola-Vargas4Rubén Burgos-Vargas5María Lilia Domínguez-López6José Pablo Romero-López7Laboratorio de Patogénesis Molecular, Edificio A4, Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla de Baz, Estado de Mexico, MexicoLaboratorio de Inmunoquímica 1, Posgrado en Ciencias Quimicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de Mexico, MexicoLaboratorio de Patogénesis Molecular, Edificio A4, Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla de Baz, Estado de Mexico, MexicoLaboratorio de Inmunoquímica 1, Posgrado en Ciencias Quimicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de Mexico, MexicoDepartment of Rheumatology Hospital General Dr. Eduardo Liceaga, Ciudad de Mexico, MexicoDepartment of Rheumatology Hospital General Dr. Eduardo Liceaga, Ciudad de Mexico, MexicoLaboratorio de Inmunoquímica 1, Posgrado en Ciencias Quimicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de Mexico, MexicoLaboratorio de Patogénesis Molecular, Edificio A4, Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla de Baz, Estado de Mexico, MexicoRegulatory T cells (Tregs) are critical for maintaining immune tolerance by suppressing effector T cell responses. However, in chronic inflammatory diseases such as spondyloarthritis (SpA) and psoriasis (PsO), Tregs can lose their stability and acquire pro-inflammatory characteristics, a phenomenon known as Treg plasticity. Under inflammatory conditions, Tregs may downregulate FoxP3, upregulate RORγt, and produce cytokines such as IL-17 and IFN-γ, thus losing their suppressive function and contributing to disease progression. In SpA, altered numbers and impaired Treg function have been identified in peripheral blood and synovial fluid. Specific subsets, such as CD161+ Tregs with Th17-like features, suggest that inflammatory cytokines and signals like STAT3 activation and ICOS engagement promote pathogenic reprogramming. Genetic factors, including HLA-B27, may further predispose Tregs to instability. Single-cell transcriptomic analyses have provided evidence of shared TCR repertoires between Tregs and effector T cells, reinforcing the concept of lineage plasticity. Similarly, in PsO, skin-resident Tregs exposed to IL-23, IL-6, and IL-21 can acquire a Th17-like phenotype, producing IL-17A and exacerbating local inflammation. Environmental factors such as hypoxia also contribute to destabilizing Treg identity. The persistence of pathogenic Tregs, even following therapy blockade of IL-17 or IL-23, highlights the challenge of achieving long-term disease remission.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621396/fullTreg cellsTreg plasticityIL-17spondyloarthritispsoriasis |
| spellingShingle | Ingrid Itzayanna Ortega-Mejia Ingrid Itzayanna Ortega-Mejia Nayeli Romero-López Nayeli Romero-López Julio César Casasola-Vargas Rubén Burgos-Vargas María Lilia Domínguez-López José Pablo Romero-López Treg cell plasticity as a driver of inflammation in spondyloarthritis and psoriasis Frontiers in Immunology Treg cells Treg plasticity IL-17 spondyloarthritis psoriasis |
| title | Treg cell plasticity as a driver of inflammation in spondyloarthritis and psoriasis |
| title_full | Treg cell plasticity as a driver of inflammation in spondyloarthritis and psoriasis |
| title_fullStr | Treg cell plasticity as a driver of inflammation in spondyloarthritis and psoriasis |
| title_full_unstemmed | Treg cell plasticity as a driver of inflammation in spondyloarthritis and psoriasis |
| title_short | Treg cell plasticity as a driver of inflammation in spondyloarthritis and psoriasis |
| title_sort | treg cell plasticity as a driver of inflammation in spondyloarthritis and psoriasis |
| topic | Treg cells Treg plasticity IL-17 spondyloarthritis psoriasis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621396/full |
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