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Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance

Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127(low) Tregs in the...

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Autores principales: Ssemaganda, Aloysious, Cholette, Francois, Perner, Michelle, Kambaran, Cheli, Adhiambo, Wendy, Wambugu, Peter M., Gebrebrhan, Henok, Lee, Amy, Nuhu, Faisal, Mwatelah, Ruth S., Jahan, Naima, Omole, Tosin E., Wanjiru, Tabitha, Gitau, Apollo, Kimani, Joshua, McKinnon, Lyle R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495419/
https://www.ncbi.nlm.nih.gov/pubmed/34630402
http://dx.doi.org/10.3389/fimmu.2021.726472
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author Ssemaganda, Aloysious
Cholette, Francois
Perner, Michelle
Kambaran, Cheli
Adhiambo, Wendy
Wambugu, Peter M.
Gebrebrhan, Henok
Lee, Amy
Nuhu, Faisal
Mwatelah, Ruth S.
Jahan, Naima
Omole, Tosin E.
Wanjiru, Tabitha
Gitau, Apollo
Kimani, Joshua
McKinnon, Lyle R.
author_facet Ssemaganda, Aloysious
Cholette, Francois
Perner, Michelle
Kambaran, Cheli
Adhiambo, Wendy
Wambugu, Peter M.
Gebrebrhan, Henok
Lee, Amy
Nuhu, Faisal
Mwatelah, Ruth S.
Jahan, Naima
Omole, Tosin E.
Wanjiru, Tabitha
Gitau, Apollo
Kimani, Joshua
McKinnon, Lyle R.
author_sort Ssemaganda, Aloysious
collection PubMed
description Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127(low) Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p<0.0001). Most Tregs expressed FOXP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log(10) CD4+ T cells per log(10) Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.
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spelling pubmed-84954192021-10-08 Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance Ssemaganda, Aloysious Cholette, Francois Perner, Michelle Kambaran, Cheli Adhiambo, Wendy Wambugu, Peter M. Gebrebrhan, Henok Lee, Amy Nuhu, Faisal Mwatelah, Ruth S. Jahan, Naima Omole, Tosin E. Wanjiru, Tabitha Gitau, Apollo Kimani, Joshua McKinnon, Lyle R. Front Immunol Immunology Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127(low) Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p<0.0001). Most Tregs expressed FOXP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log(10) CD4+ T cells per log(10) Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women. Frontiers Media S.A. 2021-09-23 /pmc/articles/PMC8495419/ /pubmed/34630402 http://dx.doi.org/10.3389/fimmu.2021.726472 Text en Copyright © 2021 Ssemaganda, Cholette, Perner, Kambaran, Adhiambo, Wambugu, Gebrebrhan, Lee, Nuhu, Mwatelah, Jahan, Omole, Wanjiru, Gitau, Kimani and McKinnon https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ssemaganda, Aloysious
Cholette, Francois
Perner, Michelle
Kambaran, Cheli
Adhiambo, Wendy
Wambugu, Peter M.
Gebrebrhan, Henok
Lee, Amy
Nuhu, Faisal
Mwatelah, Ruth S.
Jahan, Naima
Omole, Tosin E.
Wanjiru, Tabitha
Gitau, Apollo
Kimani, Joshua
McKinnon, Lyle R.
Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance
title Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance
title_full Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance
title_fullStr Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance
title_full_unstemmed Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance
title_short Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance
title_sort endocervical regulatory t cells are associated with decreased genital inflammation and lower hiv target cell abundance
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495419/
https://www.ncbi.nlm.nih.gov/pubmed/34630402
http://dx.doi.org/10.3389/fimmu.2021.726472
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