Cargando…
CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions
We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modi...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233694/ https://www.ncbi.nlm.nih.gov/pubmed/34195685 http://dx.doi.org/10.1016/j.xcrm.2021.100322 |
_version_ | 1783713908577533952 |
---|---|
author | Richert-Spuhler, Laura E. Mar, Corinne M. Shinde, Paurvi Wu, Feinan Hong, Ting Greene, Evan Hou, Sharon Thomas, Katherine Gottardo, Raphael Mugo, Nelly de Bruyn, Guy Celum, Connie Baeten, Jared M. Lingappa, Jairam R. Lund, Jennifer M. |
author_facet | Richert-Spuhler, Laura E. Mar, Corinne M. Shinde, Paurvi Wu, Feinan Hong, Ting Greene, Evan Hou, Sharon Thomas, Katherine Gottardo, Raphael Mugo, Nelly de Bruyn, Guy Celum, Connie Baeten, Jared M. Lingappa, Jairam R. Lund, Jennifer M. |
author_sort | Richert-Spuhler, Laura E. |
collection | PubMed |
description | We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets. |
format | Online Article Text |
id | pubmed-8233694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-82336942021-06-29 CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions Richert-Spuhler, Laura E. Mar, Corinne M. Shinde, Paurvi Wu, Feinan Hong, Ting Greene, Evan Hou, Sharon Thomas, Katherine Gottardo, Raphael Mugo, Nelly de Bruyn, Guy Celum, Connie Baeten, Jared M. Lingappa, Jairam R. Lund, Jennifer M. Cell Rep Med Article We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets. Elsevier 2021-06-15 /pmc/articles/PMC8233694/ /pubmed/34195685 http://dx.doi.org/10.1016/j.xcrm.2021.100322 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Richert-Spuhler, Laura E. Mar, Corinne M. Shinde, Paurvi Wu, Feinan Hong, Ting Greene, Evan Hou, Sharon Thomas, Katherine Gottardo, Raphael Mugo, Nelly de Bruyn, Guy Celum, Connie Baeten, Jared M. Lingappa, Jairam R. Lund, Jennifer M. CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions |
title | CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions |
title_full | CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions |
title_fullStr | CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions |
title_full_unstemmed | CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions |
title_short | CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions |
title_sort | cd101 genetic variants modify regulatory and conventional t cell phenotypes and functions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233694/ https://www.ncbi.nlm.nih.gov/pubmed/34195685 http://dx.doi.org/10.1016/j.xcrm.2021.100322 |
work_keys_str_mv | AT richertspuhlerlaurae cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT marcorinnem cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT shindepaurvi cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT wufeinan cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT hongting cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT greeneevan cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT housharon cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT thomaskatherine cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT gottardoraphael cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT mugonelly cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT debruynguy cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT celumconnie cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT baetenjaredm cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT lingappajairamr cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT lundjenniferm cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions AT cd101geneticvariantsmodifyregulatoryandconventionaltcellphenotypesandfunctions |