Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ
| العنوان: | Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ |
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| المؤلفون: | Sigrid Fra-Bido, Louise S. Matheson, Julien Novarino, Noudjoud Attaf, Silvia Innocentin, Nicolas Fazilleau, Louise M. C. Webb, Alexandre Bignon, Michelle A. Linterman |
| المساهمون: | Benson-Rumiz, Alicia, The Babraham Institute [Cambridge, UK], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Webb, Louise MC [0000-0003-3417-1484], Fra-Bido, Sigrid [0000-0003-2398-5191], Attaf, Noudjoud [0000-0001-7254-7679], Fazilleau, Nicolas [0000-0002-3574-5614], Linterman, Michelle A [0000-0001-6047-1996], Apollo - University of Cambridge Repository |
| المصدر: | Aging Cell Aging Cell, 2021, 20 (1), pp.e13295. ⟨10.1111/acel.13295⟩ |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Receptors, CXCR5, Aging, Notch, T Follicular Helper Cells, Cellular differentiation, Biology, RBPJ, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Animals, Humans, Transcription factor, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, T follicular helper cell differentiation, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Effector, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, T-cell receptor, Cell Differentiation, Cell Biology, Original Articles, Cell biology, CXCR5, 030104 developmental biology, age, Ageing, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Female, Original Article, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery |
| الوصف: | Ageing profoundly changes our immune system and is thought to be a driving factor in the morbidity and mortality associated with infectious disease in older people. We have previously shown that the impaired immunity to vaccination that occurs in aged individuals is partly attributed to the effect of age on T follicular helper (Tfh) cell formation. In this study, we examined how age intrinsically affects Tfh cell formation in both mice and humans. We show increased formation of Tfh precursors (pre‐Tfh) but no associated increase in germinal centre (GC)‐Tfh cells in aged mice, suggesting age‐driven promotion of only early Tfh cell differentiation. Mechanistically, we show that ageing alters TCR signalling which drives expression of the Notch‐associated transcription factor, RBPJ. Genetic or chemical modulation of RBPJ or Notch rescues this age‐associated early Tfh cell differentiation, and increased intrinsic Notch activity recapitulates this phenomenon in younger mice. Our data offer mechanistic insight into the age‐induced changes in T‐cell activation that affects the differentiation and ultimately the function of effector T cells. Ageing alters TCR signalling which drives expression of the Notch‐associated transcription factor, RBPJ. This results in enhanced differentiation into T follicular helper cell precursors. |
| وصف الملف: | application/pdf |
| تدمد: | 1474-9726 1474-9718 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::378a26386c2b4bd93dd57f43ea8d4b33 https://pubmed.ncbi.nlm.nih.gov/33387451 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....378a26386c2b4bd93dd57f43ea8d4b33 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14749726 14749718 |
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