@article{64adc39873824c10a28a65c776d565e0,
title = "Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging",
abstract = "The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older individuals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (TFH) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that TFH cell localization is critical for the quality of the antibody response and for the expansion of the FDC network upon immunization. The smaller GC and compressed FDC network in aged mice were corrected by provision of TFH cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that TFH cells support stromal cell responses to vaccines.",
author = "Alyssa Silva-Cayetano and Sigrid Fra-Bido and Robert, {Philippe A.} and Silvia Innocentin and Burton, {Alice R.} and Watson, {Emily M.} and Lee, {Jia Le} and Webb, {Louise M.C.} and Foster, {William S.} and McKenzie, {Ross C.J.} and Alexandre Bignon and Ine Vanderleyden and Dominik Alterauge and Lemos, {Julia P.} and Carr, {Edward J.} and Hill, {Danika L.} and Isabella Cinti and Karl Balabanian and Dirk Baumjohann and Marion Espeli and Michael Meyer-Hermann and Denton, {Alice E.} and Linterman, {Michelle A.}",
note = "Funding Information: We thank C. Vinuesa and A. Liston for critical feedback on this paper. We thank the Babraham Institute Biological Support Unit staff, who performed in vivo treatments of our animals and took care of animal husbandry. We thank the staff of the Babraham Flow Cytometry and Imaging Facilities for their technical support. The National Institute for Health Research Cambridge Biomedical Research Center is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by the National Institute for Health Research. We thank the National Institute for Health Research Cambridge Biomedical Research Center volunteers for their participation and thank staff for their contribution in coordinating the vaccinations and venipuncture. This study was supported by funding from the Biotechnology and Biological Sciences Research Council (grant nos. BB/W001578/1, BBS/E/B/000C0407, BBS/E/B/000C0427 to M.A.L.; grant no. BBSRC BB/N011740/1 to A.E.D; and the Campus Capability Core Grant to the Babraham Institute), the European Union{\textquoteright}s Horizon 2020 research and innovation program {\textquoteleft}ENLIGHT-TEN{\textquoteright} under the Marie Sklodowska-Curie grant agreement no. 675395 to M.A.L., a grant from IdEx Universit{\'e} de Paris (grant no. ANR-18-IDEX-0001 to M.E.) and by an ANR PRC grant (grant no. ANR-17-CE14-0019 to K.B.). M.A.L. is an EMBO Young Investigator and a Lister Institute Prize Fellow. D.B. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Emmy Noether Programs BA 5132/1-1 and BA 5132/1-2 (grant no. 252623821 to D.B.), SFB 1054 Project B12 (grant no. 210592381 to D.B.) and Germany{\textquoteright}s Excellence Strategy EXC2151 (grant no. 390873048 to D.B.). P.A.R. was supported by the Human Frontier Science Program (grant no. RGP0033/2015 to P.A.R.) and a PhD fellowship granted by {\'E}cole Normale Sup{\'e}rieure de Lyon. J.L.L. is supported by a National Science Scholarship (PhD) by the Agency for Science, Technology and Research, Singapore. D.L.H. received a National Health and Medical Research Council Australia Early-Career Fellowship (grant no. APP1139911). A.R.B. received a Sir Henry Wellcome Postdoctoral Fellowship (grant no. 222793/Z/21/Z). J.P.L. was a recipient of the People Program (Marie Curie Actions) of the European Union{\textquoteright}s Seventh Framework Program (FP7/2007-2013) under REA grant agreement no. PCOFUND-GA-2013-609102. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = jul,
doi = "10.1038/s41590-023-01519-9",
language = "English",
volume = "24",
pages = "1124--1137+",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "7",
}
