CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions
Summary: 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 vari...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Cell Reports Medicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379121001658 |
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English |
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Laura E. Richert-Spuhler Corinne M. Mar Paurvi Shinde Feinan Wu Ting Hong Evan Greene Sharon Hou Katherine Thomas Raphael Gottardo Nelly Mugo Guy de Bruyn Connie Celum Jared M. Baeten Jairam R. Lingappa Jennifer M. Lund Connie Celum Anna Wald Jairam R. Lingappa Jared M. Baeten Mary S. Campbell Lawrence Corey Robert W. Coombs James P. Hughes Amalia Magaret M. Juliana McElrath Rhoda Morrow James I. Mullins David Coetzee Kenneth Fife Edwin Were Max Essex Joseph Makhema Elly Katabira Allan Ronald Elizabeth Bukusi Craig Cohen Saidi Kapiga Rachel Manongi Carey Farquhar Grace John-Stewart James Kiarie Sinead Delany-Moretlwe Helen Rees Guy de Bruyn Glenda Gray James McIntyre Nelly Rwamba Mugo Connie Celum Jared M. Baeten Deborah Donnell Robert W. Coombs Lisa Frenkel Craig W. Hendrix Jairam R. Lingappa M. Juliana McElrath Kenneth Fife Edwin Were Elioda Tumwesigye Patrick Ndase Elly Katabira Allan Ronald Eliabeth Bukusi Craig Cohen Jonathan Wangisi James Campbell Jordan Tappero James Kiarie Carey Farquhar Grace John-Stewart Nelly Rwamba Mugo |
| spellingShingle |
Laura E. Richert-Spuhler Corinne M. Mar Paurvi Shinde Feinan Wu Ting Hong Evan Greene Sharon Hou Katherine Thomas Raphael Gottardo Nelly Mugo Guy de Bruyn Connie Celum Jared M. Baeten Jairam R. Lingappa Jennifer M. Lund Connie Celum Anna Wald Jairam R. Lingappa Jared M. Baeten Mary S. Campbell Lawrence Corey Robert W. Coombs James P. Hughes Amalia Magaret M. Juliana McElrath Rhoda Morrow James I. Mullins David Coetzee Kenneth Fife Edwin Were Max Essex Joseph Makhema Elly Katabira Allan Ronald Elizabeth Bukusi Craig Cohen Saidi Kapiga Rachel Manongi Carey Farquhar Grace John-Stewart James Kiarie Sinead Delany-Moretlwe Helen Rees Guy de Bruyn Glenda Gray James McIntyre Nelly Rwamba Mugo Connie Celum Jared M. Baeten Deborah Donnell Robert W. Coombs Lisa Frenkel Craig W. Hendrix Jairam R. Lingappa M. Juliana McElrath Kenneth Fife Edwin Were Elioda Tumwesigye Patrick Ndase Elly Katabira Allan Ronald Eliabeth Bukusi Craig Cohen Jonathan Wangisi James Campbell Jordan Tappero James Kiarie Carey Farquhar Grace John-Stewart Nelly Rwamba Mugo CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions Cell Reports Medicine CD101 inflammation immune quiescence inflammatory homeostasis T cell host genetic variation |
| author_facet |
Laura E. Richert-Spuhler Corinne M. Mar Paurvi Shinde Feinan Wu Ting Hong Evan Greene Sharon Hou Katherine Thomas Raphael Gottardo Nelly Mugo Guy de Bruyn Connie Celum Jared M. Baeten Jairam R. Lingappa Jennifer M. Lund Connie Celum Anna Wald Jairam R. Lingappa Jared M. Baeten Mary S. Campbell Lawrence Corey Robert W. Coombs James P. Hughes Amalia Magaret M. Juliana McElrath Rhoda Morrow James I. Mullins David Coetzee Kenneth Fife Edwin Were Max Essex Joseph Makhema Elly Katabira Allan Ronald Elizabeth Bukusi Craig Cohen Saidi Kapiga Rachel Manongi Carey Farquhar Grace John-Stewart James Kiarie Sinead Delany-Moretlwe Helen Rees Guy de Bruyn Glenda Gray James McIntyre Nelly Rwamba Mugo Connie Celum Jared M. Baeten Deborah Donnell Robert W. Coombs Lisa Frenkel Craig W. Hendrix Jairam R. Lingappa M. Juliana McElrath Kenneth Fife Edwin Were Elioda Tumwesigye Patrick Ndase Elly Katabira Allan Ronald Eliabeth Bukusi Craig Cohen Jonathan Wangisi James Campbell Jordan Tappero James Kiarie Carey Farquhar Grace John-Stewart Nelly Rwamba Mugo |
| author_sort |
Laura E. Richert-Spuhler |
| title |
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_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_sort |
cd101 genetic variants modify regulatory and conventional t cell phenotypes and functions |
| publisher |
Elsevier |
| series |
Cell Reports Medicine |
| issn |
2666-3791 |
| publishDate |
2021-06-01 |
| description |
Summary: 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. |
| topic |
CD101 inflammation immune quiescence inflammatory homeostasis T cell host genetic variation |
| url |
http://www.sciencedirect.com/science/article/pii/S2666379121001658 |
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1721374314086793216 |
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doaj-77c9c8a5edec4baab70c11a3ba3a103b2021-06-17T04:48:49ZengElsevierCell Reports Medicine2666-37912021-06-0126100322CD101 genetic variants modify regulatory and conventional T cell phenotypes and functionsLaura E. Richert-Spuhler0Corinne M. Mar1Paurvi Shinde2Feinan Wu3Ting Hong4Evan Greene5Sharon Hou6Katherine Thomas7Raphael Gottardo8Nelly Mugo9Guy de Bruyn10Connie Celum11Jared M. Baeten12Jairam R. Lingappa13Jennifer M. Lund14Connie CelumAnna WaldJairam R. LingappaJared M. BaetenMary S. CampbellLawrence CoreyRobert W. CoombsJames P. HughesAmalia MagaretM. Juliana McElrathRhoda MorrowJames I. MullinsDavid CoetzeeKenneth FifeEdwin WereMax EssexJoseph MakhemaElly KatabiraAllan RonaldElizabeth BukusiCraig CohenSaidi KapigaRachel ManongiCarey FarquharGrace John-StewartJames KiarieSinead Delany-MoretlweHelen ReesGuy de BruynGlenda GrayJames McIntyreNelly Rwamba MugoConnie CelumJared M. BaetenDeborah DonnellRobert W. CoombsLisa FrenkelCraig W. HendrixJairam R. LingappaM. Juliana McElrathKenneth FifeEdwin WereElioda TumwesigyePatrick NdaseElly KatabiraAllan RonaldEliabeth BukusiCraig CohenJonathan WangisiJames CampbellJordan TapperoJames KiarieCarey FarquharGrace John-StewartNelly Rwamba MugoVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADepartment of Global Health, University of Washington, Seattle, WA 98104, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USAGenomics & Bioinformatics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADepartment of Global Health, University of Washington, Seattle, WA 98104, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADepartment of Global Health, University of Washington, Seattle, WA 98104, USADepartment of Global Health, University of Washington, Seattle, WA 98104, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADepartment of Global Health, University of Washington, Seattle, WA 98104, USA; Kenya Medical Research Institute, Nairobi, KenyaPerinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South AfricaDepartment of Global Health, University of Washington, Seattle, WA 98104, USA; Department of Medicine, University of Washington, Seattle, WA 98104, USA; Department of Epidemiology, University of Washington, Seattle, WA 98104, USADepartment of Global Health, University of Washington, Seattle, WA 98104, USA; Department of Medicine, University of Washington, Seattle, WA 98104, USA; Department of Epidemiology, University of Washington, Seattle, WA 98104, USADepartment of Global Health, University of Washington, Seattle, WA 98104, USA; Department of Medicine, University of Washington, Seattle, WA 98104, USA; Department of Pediatrics, University of Washington, Seattle, WA 98104, USA; Corresponding authorVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98104, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666379121001658CD101inflammationimmune quiescenceinflammatory homeostasisT cellhost genetic variation |