Developmental bifurcation of human T follicular regulatory cells.

Autor: Kumar S; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Fonseca VR; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.; Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal., Ribeiro F; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Basto AP; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Água-Doce A; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Monteiro M; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Elessa D; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Miragaia RJ; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Gomes T; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Piaggio E; Institut Curie, PSL Research University, INSERM U932, Paris F-75005, France.; Centre d'Investigation Clinique Biotherapie CICBT 1428, Institut Curie, Paris F-75005, France., Segura E; Institut Curie, PSL Research University, INSERM U932, Paris F-75005, France., Gama-Carvalho M; BioISI - Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Lisboa 1749-016, Portugal., Teichmann SA; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.; Theory of Condensed Matter Group, Cavendish Laboratory/Department of Physics, University of Cambridge, JJ Thomson Ave., Cambridge CB3 0HE, UK., Graca L; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. lgraca@medicina.ulisboa.pt.; Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2021 May 28; Vol. 6 (59).
DOI: 10.1126/sciimmunol.abd8411
Abstrakt: Germinal centers (GCs) are anatomic structures where B cells undergo affinity maturation, leading to production of high-affinity antibodies. The balance between T follicular helper (T FH ) and regulatory (T FR ) cells is critical for adequate control of GC responses. The study of human T FH and T FR cell development has been hampered because of the lack of in vitro assays reproducing in vivo biology, along with difficult access to healthy human lymphoid tissues. We used a single-cell transcriptomics approach to study the maturation of T FH and T FR cells isolated from human blood, iliac lymph nodes (LNs), and tonsils. As independent tissues have distinct proportions of follicular T cells in different maturation states, we leveraged the heterogeneity to reconstruct the maturation trajectory for human T FH and T FR cells. We found that the dominant maturation of T FR cells follows a bifurcated trajectory from precursor T reg cells, with one arm of the bifurcation leading to blood T FR cells and the other leading to the most mature GC T FR cells. Overall, our data provide a comprehensive resource for the transcriptomics of different follicular T cell populations and their dynamic relationship across different tissues.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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