11-deoxycortisol positively correlates with T cell immune traits in physiological conditionsResearch in context
Summary: Background: Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored. Methods: We conducted a systematic approach to examine the association between steroid hormones p...
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Elsevier
2024-01-01
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Series: | EBioMedicine |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423005017 |
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author | Chunying Peng Xun Jiang Martin Jaeger Pepijn van Houten Antonius E. van Herwaarden Valerie A.C.M. Koeken Simone J.C.F.M. Moorlag Vera P. Mourits Heidi Lemmers Helga Dijkstra Hans J.P.M. Koenen Irma Joosten Bram van Cranenbroek Yang Li Leo A.B. Joosten Mihai G. Netea Romana T. Netea-Maier Cheng-Jian Xu |
author_facet | Chunying Peng Xun Jiang Martin Jaeger Pepijn van Houten Antonius E. van Herwaarden Valerie A.C.M. Koeken Simone J.C.F.M. Moorlag Vera P. Mourits Heidi Lemmers Helga Dijkstra Hans J.P.M. Koenen Irma Joosten Bram van Cranenbroek Yang Li Leo A.B. Joosten Mihai G. Netea Romana T. Netea-Maier Cheng-Jian Xu |
author_sort | Chunying Peng |
collection | DOAJ |
description | Summary: Background: Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored. Methods: We conducted a systematic approach to examine the association between steroid hormones profile and immune traits in a cohort of 534 healthy volunteers. Serum concentrations of steroid hormones and their precursors (cortisol, progesterone, testosterone, androstenedione, 11-deoxycortisol and 17-OH progesterone) were determined by liquid chromatography-tandem mass spectrometry. Immune traits were evaluated by quantifying cellular composition of the circulating immune system and ex vivo cytokine responses elicited by major human pathogens and microbial ligands. An independent cohort of 321 individuals was used for validation, followed by in vitro validation experiments. Findings: We observed a positive association between 11-deoxycortisol and lymphoid cellular subsets numbers and function (especially IL-17 response). The association with lymphoid cellularity was validated in an independent validation cohort. In vitro experiments showed that, as compared to androstenedione and 17-OH progesterone, 11-deoxycortisol promoted T cell proliferation and Candida-induced Th17 polarization at physiologically relevant concentrations. Functionally, 11-deoxycortisol-treated T cells displayed a more activated phenotype (PD-L1high CD25high CD62Llow CD127low) in response to CD3/CD28 co-stimulation, and downregulated expression of T-bet nuclear transcription factor. Interpretation: Our findings suggest a positive association between 11-deoxycortisol and T-cell function under physiological conditions. Further investigation is needed to explore the potential mechanisms and clinical implications. Funding: Found in acknowledgements. |
first_indexed | 2024-03-08T21:12:44Z |
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id | doaj.art-c4da9316b306442c8b252dd413d97213 |
institution | Directory Open Access Journal |
issn | 2352-3964 |
language | English |
last_indexed | 2024-03-08T21:12:44Z |
publishDate | 2024-01-01 |
publisher | Elsevier |
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series | EBioMedicine |
spelling | doaj.art-c4da9316b306442c8b252dd413d972132023-12-22T05:33:25ZengElsevierEBioMedicine2352-39642024-01-019910493511-deoxycortisol positively correlates with T cell immune traits in physiological conditionsResearch in contextChunying Peng0Xun Jiang1Martin Jaeger2Pepijn van Houten3Antonius E. van Herwaarden4Valerie A.C.M. Koeken5Simone J.C.F.M. Moorlag6Vera P. Mourits7Heidi Lemmers8Helga Dijkstra9Hans J.P.M. Koenen10Irma Joosten11Bram van Cranenbroek12Yang Li13Leo A.B. Joosten14Mihai G. Netea15Romana T. Netea-Maier16Cheng-Jian Xu17Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsCentre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, GermanyDivision of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the NetherlandsDivision of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsCentre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Research Centre Innovations in Care, Rotterdam University of Applied Science, Rotterdam, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the NetherlandsLaboratory Medical Immunology, Radboud University Medical Center, Nijmegen, the NetherlandsLaboratory Medical Immunology, Radboud University Medical Center, Nijmegen, the NetherlandsLaboratory Medical Immunology, Radboud University Medical Center, Nijmegen, the NetherlandsCentre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the NetherlandsDivision of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Corresponding author.Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Corresponding author. Centre for Individualized Infection Medicine (CiiM), Feodor-Lynen-Street 7, 30625, Hannover, Germany.Summary: Background: Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored. Methods: We conducted a systematic approach to examine the association between steroid hormones profile and immune traits in a cohort of 534 healthy volunteers. Serum concentrations of steroid hormones and their precursors (cortisol, progesterone, testosterone, androstenedione, 11-deoxycortisol and 17-OH progesterone) were determined by liquid chromatography-tandem mass spectrometry. Immune traits were evaluated by quantifying cellular composition of the circulating immune system and ex vivo cytokine responses elicited by major human pathogens and microbial ligands. An independent cohort of 321 individuals was used for validation, followed by in vitro validation experiments. Findings: We observed a positive association between 11-deoxycortisol and lymphoid cellular subsets numbers and function (especially IL-17 response). The association with lymphoid cellularity was validated in an independent validation cohort. In vitro experiments showed that, as compared to androstenedione and 17-OH progesterone, 11-deoxycortisol promoted T cell proliferation and Candida-induced Th17 polarization at physiologically relevant concentrations. Functionally, 11-deoxycortisol-treated T cells displayed a more activated phenotype (PD-L1high CD25high CD62Llow CD127low) in response to CD3/CD28 co-stimulation, and downregulated expression of T-bet nuclear transcription factor. Interpretation: Our findings suggest a positive association between 11-deoxycortisol and T-cell function under physiological conditions. Further investigation is needed to explore the potential mechanisms and clinical implications. Funding: Found in acknowledgements.http://www.sciencedirect.com/science/article/pii/S2352396423005017Immune homeostasisSteroid hormones11-deoxycortisolT cell proliferationTh17 |
spellingShingle | Chunying Peng Xun Jiang Martin Jaeger Pepijn van Houten Antonius E. van Herwaarden Valerie A.C.M. Koeken Simone J.C.F.M. Moorlag Vera P. Mourits Heidi Lemmers Helga Dijkstra Hans J.P.M. Koenen Irma Joosten Bram van Cranenbroek Yang Li Leo A.B. Joosten Mihai G. Netea Romana T. Netea-Maier Cheng-Jian Xu 11-deoxycortisol positively correlates with T cell immune traits in physiological conditionsResearch in context EBioMedicine Immune homeostasis Steroid hormones 11-deoxycortisol T cell proliferation Th17 |
title | 11-deoxycortisol positively correlates with T cell immune traits in physiological conditionsResearch in context |
title_full | 11-deoxycortisol positively correlates with T cell immune traits in physiological conditionsResearch in context |
title_fullStr | 11-deoxycortisol positively correlates with T cell immune traits in physiological conditionsResearch in context |
title_full_unstemmed | 11-deoxycortisol positively correlates with T cell immune traits in physiological conditionsResearch in context |
title_short | 11-deoxycortisol positively correlates with T cell immune traits in physiological conditionsResearch in context |
title_sort | 11 deoxycortisol positively correlates with t cell immune traits in physiological conditionsresearch in context |
topic | Immune homeostasis Steroid hormones 11-deoxycortisol T cell proliferation Th17 |
url | http://www.sciencedirect.com/science/article/pii/S2352396423005017 |
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