Exploring the differential functions of circulating follicular helper T and peripheral helper T cells in rheumatoid arthritis based on metabolism patterns Article Swipe
Ziran Bai
,
Siwen Yang
,
Jinyi Ren
,
Cheng Zhang
,
Xianmei Chen
,
Huina Huang
,
Guan Wang
,
Yawei Tang
,
Jingjing Qi
,
Xia Li
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2025.1608675
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2025.1608675
Introduction The number of circulating follicular helper T (cTfh) and peripheral helper T (Tph) cells is elevated in rheumatoid arthritis (RA), yet the molecular mechanisms mediating their specific contributions to RA pathology remain unclear. In this study, we explored the distinct function of cTfh and Tph cells based on metabolism patterns in RA. Methods Peripheral CD4+ T cells from RA patients were treated with CXCL13 or CCL2, glycolysis inhibitor 2-DG or mitochondria-targeted antioxidant MitoQ in vitro . Collagen induced arthritis (CIA) mice were treated with 2-DG or MitoQ in vivo . The frequency, transcription factors, functional molecules, cellular senescence, glycolytic activity and mitochondrial ROS (mtROS) of cTfh and Tph cells were assessed. Joint inflammation, CD4+PD-1+ T cells, glycolytic enzymes or IL-1β and IL-6 in ankle joints of CIA mice were detected. Results We found that in RA patients, in comparison with Tph cells, cTfh cells show higher levels of Bcl6 and BATF, B helper-related molecules, and glycolytic activity. While Tph cells exhibit higher levels of Blimp1 and T-bet, cytotoxicity-related molecules and mtROS, and more significant cellular senescence characteristics. In addition, CXCL13, the ligand for CXCR5, increases the expression of key glycolytic enzymes in RA cTfh cells, while CCL2 increases mtROS in RA Tph cells. 2-DG reduces the expression of B helper-related molecules cells, and MitoQ mitigates cytotoxic activity of cTfh and Tph cells. Both treatments ameliorate RA symptoms and decrease the number of cTfh and Tph cells in CIA mice. Conclusion Our study suggests that in RA patients, cTfh cells display a more robust B helper-associated function, potentially linked to the CXCL13-CXCR5 axis enhancing glycolysis. Tph cells, on the other hand, show greater cytotoxic activity, possibly due to the CCL2-CCR2 axis increasing mtROS production. Targeting glycolysis or mtROS may offer a novel therapeutic strategy for RA patients.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2025.1608675
- https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1608675/pdf
- OA Status
- gold
- Cited By
- 1
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4411389076
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4411389076Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2025.1608675Digital Object Identifier
- Title
-
Exploring the differential functions of circulating follicular helper T and peripheral helper T cells in rheumatoid arthritis based on metabolism patternsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-06-17Full publication date if available
- Authors
-
Ziran Bai, Siwen Yang, Jinyi Ren, Cheng Zhang, Xianmei Chen, Huina Huang, Guan Wang, Yawei Tang, Jingjing Qi, Xia LiList of authors in order
- Landing page
-
https://doi.org/10.3389/fimmu.2025.1608675Publisher landing page
- PDF URL
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https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1608675/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1608675/pdfDirect OA link when available
- Concepts
-
Rheumatoid arthritis, Immunology, Follicular phase, Peripheral blood, Medicine, Peripheral, Endocrinology, Internal medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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51Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.helper | 6, 11 |
| abstract_inverted_index.higher | 146, 162 |
| abstract_inverted_index.joints | 125 |
| abstract_inverted_index.levels | 147, 163 |
| abstract_inverted_index.ligand | 182 |
| abstract_inverted_index.linked | 258 |
| abstract_inverted_index.mtROS, | 171 |
| abstract_inverted_index.number | 2, 231 |
| abstract_inverted_index.remain | 32 |
| abstract_inverted_index.robust | 253 |
| abstract_inverted_index.study, | 36 |
| abstract_inverted_index.(mtROS) | 104 |
| abstract_inverted_index.CXCL13, | 180 |
| abstract_inverted_index.Methods | 53 |
| abstract_inverted_index.Results | 131 |
| abstract_inverted_index.display | 250 |
| abstract_inverted_index.enzymes | 118, 191 |
| abstract_inverted_index.exhibit | 161 |
| abstract_inverted_index.greater | 272 |
| abstract_inverted_index.induced | 78 |
| abstract_inverted_index.reduces | 205 |
| abstract_inverted_index.treated | 62, 83 |
| abstract_inverted_index.Collagen | 77 |
| abstract_inverted_index.activity | 100, 217 |
| abstract_inverted_index.cellular | 97, 175 |
| abstract_inverted_index.decrease | 229 |
| abstract_inverted_index.distinct | 40 |
| abstract_inverted_index.elevated | 16 |
| abstract_inverted_index.explored | 38 |
| abstract_inverted_index.factors, | 94 |
| abstract_inverted_index.function | 41 |
| abstract_inverted_index.patients | 60 |
| abstract_inverted_index.patterns | 50 |
| abstract_inverted_index.possibly | 275 |
| abstract_inverted_index.specific | 27 |
| abstract_inverted_index.strategy | 293 |
| abstract_inverted_index.suggests | 243 |
| abstract_inverted_index.symptoms | 227 |
| abstract_inverted_index.unclear. | 33 |
| abstract_inverted_index.CCL2-CCR2 | 279 |
| abstract_inverted_index.CD4+PD-1+ | 114 |
| abstract_inverted_index.Targeting | 284 |
| abstract_inverted_index.activity, | 274 |
| abstract_inverted_index.activity. | 157 |
| abstract_inverted_index.addition, | 179 |
| abstract_inverted_index.arthritis | 19, 79 |
| abstract_inverted_index.assessed. | 111 |
| abstract_inverted_index.cytotoxic | 216, 273 |
| abstract_inverted_index.detected. | 130 |
| abstract_inverted_index.enhancing | 263 |
| abstract_inverted_index.function, | 256 |
| abstract_inverted_index.increases | 185, 198 |
| abstract_inverted_index.inhibitor | 68 |
| abstract_inverted_index.mediating | 25 |
| abstract_inverted_index.mitigates | 215 |
| abstract_inverted_index.molecular | 23 |
| abstract_inverted_index.molecules | 169, 211 |
| abstract_inverted_index.pathology | 31 |
| abstract_inverted_index.patients, | 137, 247 |
| abstract_inverted_index.patients. | 296 |
| abstract_inverted_index.Conclusion | 240 |
| abstract_inverted_index.Peripheral | 54 |
| abstract_inverted_index.ameliorate | 225 |
| abstract_inverted_index.comparison | 139 |
| abstract_inverted_index.expression | 187, 207 |
| abstract_inverted_index.follicular | 5 |
| abstract_inverted_index.frequency, | 92 |
| abstract_inverted_index.functional | 95 |
| abstract_inverted_index.glycolysis | 67, 285 |
| abstract_inverted_index.glycolytic | 99, 117, 156, 190 |
| abstract_inverted_index.increasing | 281 |
| abstract_inverted_index.mechanisms | 24 |
| abstract_inverted_index.metabolism | 49 |
| abstract_inverted_index.molecules, | 96, 154 |
| abstract_inverted_index.peripheral | 10 |
| abstract_inverted_index.rheumatoid | 18 |
| abstract_inverted_index.senescence | 176 |
| abstract_inverted_index.treatments | 224 |
| abstract_inverted_index.antioxidant | 72 |
| abstract_inverted_index.circulating | 4 |
| abstract_inverted_index.glycolysis. | 264 |
| abstract_inverted_index.potentially | 257 |
| abstract_inverted_index.production. | 283 |
| abstract_inverted_index.senescence, | 98 |
| abstract_inverted_index.significant | 174 |
| abstract_inverted_index.therapeutic | 292 |
| abstract_inverted_index.CXCL13-CXCR5 | 261 |
| abstract_inverted_index.Introduction | 0 |
| abstract_inverted_index.contributions | 28 |
| abstract_inverted_index.inflammation, | 113 |
| abstract_inverted_index.mitochondrial | 102 |
| abstract_inverted_index.transcription | 93 |
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| abstract_inverted_index.characteristics. | 177 |
| abstract_inverted_index.helper-associated | 255 |
| abstract_inverted_index.cytotoxicity-related | 168 |
| abstract_inverted_index.mitochondria-targeted | 71 |
| cited_by_percentile_year.max | 95 |
| cited_by_percentile_year.min | 91 |
| corresponding_author_ids | https://openalex.org/A5103073845, https://openalex.org/A5045581422, https://openalex.org/A5075716817 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 10 |
| corresponding_institution_ids | https://openalex.org/I191996457, https://openalex.org/I4210100868 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.5299999713897705 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.80852406 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |