Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population
Innate lymphoid cell (ILC) lineages mirror those of CD4+ T helper cell subsets, producing type 1, 2 and 3 cytokines respectively. Studies in adult human populations have shown contributions of non-cytotoxic ILC to immune regulation or pathogenesis in a wide range of diseases and have prompted invest...
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doaj-7e6f5e61f44348e88629c7734b2e785e2020-12-08T08:37:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.594107594107Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African PopulationAlansana Darboe0Alansana Darboe1Carolyn M. Nielsen2Asia-Sophia Wolf3Jacob Wildfire4Ebrima Danso5Bakary Sonko6Christian Bottomley7Sophie E. Moore8Sophie E. Moore9Eleanor M. Riley10Martin R. Goodier11Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United KingdomVaccines & Immunity Theme, Infant Immunology, MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, GambiaNuffield Department of Medicine, University of Oxford, Oxford, United KingdomDivision of Infection and Immunity, University College London, London, United KingdomDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London, United KingdomNutrition Theme, MRC International Group, MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Keneba, GambiaNutrition Theme, MRC International Group, MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Keneba, GambiaDepartment of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United KingdomNutrition Theme, MRC International Group, MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Keneba, GambiaWomen & Children’s Health, Kings College London, London, United KingdomInstitute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London, United KingdomInnate lymphoid cell (ILC) lineages mirror those of CD4+ T helper cell subsets, producing type 1, 2 and 3 cytokines respectively. Studies in adult human populations have shown contributions of non-cytotoxic ILC to immune regulation or pathogenesis in a wide range of diseases and have prompted investigations of potential functional redundancy between ILC and T helper cell compartments in neonates and children. To investigate the potential for ILC to contribute to immune responses across the human lifespan, we examined the numbers and frequencies of peripheral blood ILC subsets in a cohort of Gambians aged between 5 and 73 years of age. ILC2 were the most abundant peripheral blood ILC subset in this Gambian cohort, while ILC1 were the rarest at all ages. Moreover, the frequency of ILC1s (as a proportion of all lymphocytes) was remarkably stable over the life course whereas ILC3 cell frequencies and absolute numbers declined steadily across the life course and ILC2 frequencies and absolute numbers declined from childhood until the age of approx. 30 years of age. Age-related reductions in ILC2 cell numbers appeared to be partially offset by increasing numbers of total and GATA3+ central memory (CD45RA-CCR7+) CD4+ T cells, although there was also a gradual decline in numbers of total and GATA3+ effector memory (CD45RA-CCR7-) CD4+ T cells. Despite reduced overall abundance of ILC2 cells, we observed a coincident increase in the proportion of CD117+ ILC2, indicating potential for age-related adaptation of these cells in childhood and early adulthood. While both CD117+ and CD117- ILC2 cells produced IL-13, these responses occurred predominantly within CD117- cells. Furthermore, comparison of ILC frequencies between aged-matched Gambian and UK young adults (25–29 years) revealed an overall higher proportion of ILC1 and ILC2, but not ILC3 in Gambians. Thus, these data indicate ongoing age-related changes in ILC2 cells throughout life, which retain the capacity to differentiate into potent type 2 cytokine producing cells, consistent with an ongoing role in immune modulation.https://www.frontiersin.org/articles/10.3389/fimmu.2020.594107/fullinnate lymphoid cellsageCD117IL-13memory CD4+ T cellsGambia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alansana Darboe Alansana Darboe Carolyn M. Nielsen Asia-Sophia Wolf Jacob Wildfire Ebrima Danso Bakary Sonko Christian Bottomley Sophie E. Moore Sophie E. Moore Eleanor M. Riley Martin R. Goodier |
spellingShingle |
Alansana Darboe Alansana Darboe Carolyn M. Nielsen Asia-Sophia Wolf Jacob Wildfire Ebrima Danso Bakary Sonko Christian Bottomley Sophie E. Moore Sophie E. Moore Eleanor M. Riley Martin R. Goodier Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population Frontiers in Immunology innate lymphoid cells age CD117 IL-13 memory CD4+ T cells Gambia |
author_facet |
Alansana Darboe Alansana Darboe Carolyn M. Nielsen Asia-Sophia Wolf Jacob Wildfire Ebrima Danso Bakary Sonko Christian Bottomley Sophie E. Moore Sophie E. Moore Eleanor M. Riley Martin R. Goodier |
author_sort |
Alansana Darboe |
title |
Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population |
title_short |
Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population |
title_full |
Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population |
title_fullStr |
Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population |
title_full_unstemmed |
Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population |
title_sort |
age-related dynamics of circulating innate lymphoid cells in an african population |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-12-01 |
description |
Innate lymphoid cell (ILC) lineages mirror those of CD4+ T helper cell subsets, producing type 1, 2 and 3 cytokines respectively. Studies in adult human populations have shown contributions of non-cytotoxic ILC to immune regulation or pathogenesis in a wide range of diseases and have prompted investigations of potential functional redundancy between ILC and T helper cell compartments in neonates and children. To investigate the potential for ILC to contribute to immune responses across the human lifespan, we examined the numbers and frequencies of peripheral blood ILC subsets in a cohort of Gambians aged between 5 and 73 years of age. ILC2 were the most abundant peripheral blood ILC subset in this Gambian cohort, while ILC1 were the rarest at all ages. Moreover, the frequency of ILC1s (as a proportion of all lymphocytes) was remarkably stable over the life course whereas ILC3 cell frequencies and absolute numbers declined steadily across the life course and ILC2 frequencies and absolute numbers declined from childhood until the age of approx. 30 years of age. Age-related reductions in ILC2 cell numbers appeared to be partially offset by increasing numbers of total and GATA3+ central memory (CD45RA-CCR7+) CD4+ T cells, although there was also a gradual decline in numbers of total and GATA3+ effector memory (CD45RA-CCR7-) CD4+ T cells. Despite reduced overall abundance of ILC2 cells, we observed a coincident increase in the proportion of CD117+ ILC2, indicating potential for age-related adaptation of these cells in childhood and early adulthood. While both CD117+ and CD117- ILC2 cells produced IL-13, these responses occurred predominantly within CD117- cells. Furthermore, comparison of ILC frequencies between aged-matched Gambian and UK young adults (25–29 years) revealed an overall higher proportion of ILC1 and ILC2, but not ILC3 in Gambians. Thus, these data indicate ongoing age-related changes in ILC2 cells throughout life, which retain the capacity to differentiate into potent type 2 cytokine producing cells, consistent with an ongoing role in immune modulation. |
topic |
innate lymphoid cells age CD117 IL-13 memory CD4+ T cells Gambia |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2020.594107/full |
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