11-deoxycortisol positively correlates with T cell immune traits in physiological conditionsResearch in context
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
Affiliations
Chunying Peng
Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
Xun Jiang
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
Martin Jaeger
Division 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 Netherlands
Pepijn van Houten
Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
Antonius E. van Herwaarden
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
Valerie A.C.M. Koeken
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; Research Centre Innovations in Care, Rotterdam University of Applied Science, Rotterdam, the Netherlands
Simone J.C.F.M. Moorlag
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
Vera P. Mourits
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
Heidi Lemmers
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
Helga Dijkstra
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
Hans J.P.M. Koenen
Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands
Irma Joosten
Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands
Bram van Cranenbroek
Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands
Yang Li
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
Leo A.B. Joosten
Department 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, Romania
Mihai G. Netea
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
Romana T. Netea-Maier
Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Corresponding author.
Cheng-Jian Xu
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.
