Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways
Summary: Humoral immune responses are dysregulated with aging, but the cellular and molecular pathways involved remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the key cells that provide help to B cells for effective h...
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Format: | Article |
Language: | English |
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Elsevier
2021-05-01
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Series: | Cell Reports Medicine |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379121000781 |
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doaj-0fb65846491c44cdad749990a1c0edc9 |
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record_format |
Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ramin Sedaghat Herati Luisa Victoria Silva Laura A. Vella Alexander Muselman Cecile Alanio Bertram Bengsch Raj K. Kurupati Senthil Kannan Sasikanth Manne Andrew V. Kossenkov David H. Canaday Susan A. Doyle Hildegund C.J. Ertl Kenneth E. Schmader E. John Wherry |
spellingShingle |
Ramin Sedaghat Herati Luisa Victoria Silva Laura A. Vella Alexander Muselman Cecile Alanio Bertram Bengsch Raj K. Kurupati Senthil Kannan Sasikanth Manne Andrew V. Kossenkov David H. Canaday Susan A. Doyle Hildegund C.J. Ertl Kenneth E. Schmader E. John Wherry Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways Cell Reports Medicine T follicular helper vaccine NF-kB aging cellular biosensors CD4 |
author_facet |
Ramin Sedaghat Herati Luisa Victoria Silva Laura A. Vella Alexander Muselman Cecile Alanio Bertram Bengsch Raj K. Kurupati Senthil Kannan Sasikanth Manne Andrew V. Kossenkov David H. Canaday Susan A. Doyle Hildegund C.J. Ertl Kenneth E. Schmader E. John Wherry |
author_sort |
Ramin Sedaghat Herati |
title |
Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways |
title_short |
Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways |
title_full |
Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways |
title_fullStr |
Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways |
title_full_unstemmed |
Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways |
title_sort |
vaccine-induced icos+cd38+ circulating tfh are sensitive biosensors of age-related changes in inflammatory pathways |
publisher |
Elsevier |
series |
Cell Reports Medicine |
issn |
2666-3791 |
publishDate |
2021-05-01 |
description |
Summary: Humoral immune responses are dysregulated with aging, but the cellular and molecular pathways involved remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the key cells that provide help to B cells for effective humoral immunity. We performed transcriptional profiling and cellular analysis on circulating Tfh before and after influenza vaccination in young and elderly adults. First, whole-blood transcriptional profiling shows that ICOS+CD38+ cTfh following vaccination preferentially enriches in gene sets associated with youth versus aging compared to other circulating T cell types. Second, vaccine-induced ICOS+CD38+ cTfh from the elderly had increased the expression of genes associated with inflammation, including tumor necrosis factor-nuclear factor κB (TNF-NF-κB) pathway activation. Finally, vaccine-induced ICOS+CD38+ cTfh display strong enrichment for signatures of underlying age-associated biological changes. These data highlight the ability to use vaccine-induced cTfh as cellular “biosensors” of underlying inflammatory and/or overall immune health. |
topic |
T follicular helper vaccine NF-kB aging cellular biosensors CD4 |
url |
http://www.sciencedirect.com/science/article/pii/S2666379121000781 |
work_keys_str_mv |
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doaj-0fb65846491c44cdad749990a1c0edc92021-05-20T07:53:11ZengElsevierCell Reports Medicine2666-37912021-05-0125100262Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathwaysRamin Sedaghat Herati0Luisa Victoria Silva1Laura A. Vella2Alexander Muselman3Cecile Alanio4Bertram Bengsch5Raj K. Kurupati6Senthil Kannan7Sasikanth Manne8Andrew V. Kossenkov9David H. Canaday10Susan A. Doyle11Hildegund C.J. Ertl12Kenneth E. Schmader13E. John Wherry14Division of Infectious Diseases and Immunology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA; Department of Microbiology, New York University School of Medicine, New York, NY, USA; Corresponding authorInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USAInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Immunology, Stanford University, Stanford, CA 94305, USAInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USADepartment of Internal Medicine II, University Medical Center Freiburg, and Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, GermanyWistar Institute, Philadelphia, PA 19104, USAWistar Institute, Philadelphia, PA 19104, USAInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USAWistar Institute, Philadelphia, PA 19104, USADivision of Infectious Disease, Case Western Reserve University, Cleveland, OH, USA; Geriatric Research, Education, and Clinical Center, Cleveland VA Medical Center, Cleveland, OH, 44195, USADivision of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC 27710, USAWistar Institute, Philadelphia, PA 19104, USADivision of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC 27710, USAInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Corresponding authorSummary: Humoral immune responses are dysregulated with aging, but the cellular and molecular pathways involved remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the key cells that provide help to B cells for effective humoral immunity. We performed transcriptional profiling and cellular analysis on circulating Tfh before and after influenza vaccination in young and elderly adults. First, whole-blood transcriptional profiling shows that ICOS+CD38+ cTfh following vaccination preferentially enriches in gene sets associated with youth versus aging compared to other circulating T cell types. Second, vaccine-induced ICOS+CD38+ cTfh from the elderly had increased the expression of genes associated with inflammation, including tumor necrosis factor-nuclear factor κB (TNF-NF-κB) pathway activation. Finally, vaccine-induced ICOS+CD38+ cTfh display strong enrichment for signatures of underlying age-associated biological changes. These data highlight the ability to use vaccine-induced cTfh as cellular “biosensors” of underlying inflammatory and/or overall immune health.http://www.sciencedirect.com/science/article/pii/S2666379121000781T follicular helpervaccineNF-kBagingcellular biosensorsCD4 |