Host and Environmental Factors Influencing Individual Human Cytokine Responses

Rob ter Horst; Martin Jaeger; Sanne P. Smeekens; Marije Oosting; Morris A. Swertz; Yang Li; Vinod Kumar; Dimitri A. Diavatopoulos; Anne F. M. Jansen; Heidi Lemmers; Helga Toenhake-Dijkstra; Antonius E. van Herwaarden; Matthijs Janssen; Renate G. van der Molen; Irma Joosten; Fred C. G. J. Sweep; Johannes W. Smit; Romana T. Netea-Maier; Mieke M. J. F. Koenders; Ramnik J. Xavier; Jos W. M. van der Meer; Charles A. Dinarello; Norman Pavelka; Cisca Wijmenga; Richard A. Notebaart; Leo A. B. Joosten; Mihai G. Netea

doi:10.1016/j.cell.2016.10.018

Host and Environmental Factors Influencing Individual Human Cytokine Responses

Rob ter Horst, Martin Jaeger, Sanne P. Smeekens, Marije Oosting, Morris A. Swertz, Yang Li, Vinod Kumar, Dimitri A. Diavatopoulos, Anne F. M. Jansen, Heidi Lemmers, Helga Toenhake-Dijkstra, Antonius E. van Herwaarden, Matthijs Janssen, Renate G. van der Molen, Irma Joosten, Fred C. G. J. Sweep, Johannes W. Smit, Romana T. Netea-Maier, Mieke M. J. F. Koenders, Ramnik J. XavierJos W. M. van der Meer, Charles A. Dinarello, Norman Pavelka, Cisca Wijmenga, Richard A. Notebaart, Leo A. B. Joosten, Mihai G. Netea

Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Research output: Contribution to journal › Article › Academic › peer-review

352 Citations (Scopus)

234 Downloads (Pure)

Abstract

Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies.

Original language	English
Pages (from-to)	1111-1124
Number of pages	14
Journal	Cell
Volume	167
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2016.10.018
Publication status	Published - 3-Nov-2016

Keywords

C-REACTIVE PROTEIN
BODY-MASS INDEX
PROGESTERONE-RECEPTOR IMMUNOREACTIVITY
ORGAN-TRANSPLANT RECIPIENTS
MULTIPLE-SCLEROSIS
IMMUNE-SYSTEM
ORAL-CONTRACEPTIVES
GENDER-DIFFERENCES
DIABETES-MELLITUS
SERUM-LEVELS

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10.1016/j.cell.2016.10.018

Host and Environmental Factors Influencing Individual Human Cytokine ResponsesFinal publisher's version, 3.08 MBLicence: Elsevier

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Additional file 22 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
Chu, X. (Contributor), Jaeger, M. (Creator), Beumer, J. (Creator), Bakker, O. (Contributor), Aguirre-Gamboa, R. (Creator), Oosting, M. (Creator), Smeekens, S. P. (Creator), Moorlag, S. (Creator), Mourits, V. P. (Creator), Koeken, V. A. C. M. (Creator), de Bree, C. (Creator), Jansen, T. (Creator), Mathews, I. T. (Creator), Dao, K. (Creator), Najhawan, M. (Creator), Watrous, J. D. (Creator), Joosten, I. (Creator), Sharma, S. (Creator), Koenen, H. J. P. M. (Creator), Withoff, S. (Creator), Jonkers, I. (Contributor), Netea-Maier, R. T. (Creator), Xavier, R. J. (Creator), Franke, L. (Contributor), Xu, C.-J. (Creator), Joosten, L. A. B. (Creator), Sanna, S. (Contributor), Jain, M. (Creator), Magadi Gopalaiah, V. K. (Contributor), Clevers, H. (Creator), Wijmenga, C. (Contributor), Netea, M. G. (Creator) & Li, Y. (Creator), figshare, 6-Jul-2021
DOI: 10.6084/m9.figshare.14921218, https://springernature.figshare.com/articles/dataset/Additional_file_22_of_Integration_of_metabolomics_genomics_and_immune_phenotypes_reveals_the_causal_roles_of_metabolites_in_disease/14921218
Dataset
Additional file 12 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
Chu, X. (Creator), Jaeger, M. (Creator), Beumer, J. (Creator), Bakker, O. (Creator), Aguirre-Gamboa, R. (Creator), Oosting, M. (Creator), Smeekens, S. P. (Creator), Moorlag, S. (Creator), Mourits, V. P. (Creator), Koeken, V. A. C. M. (Creator), de Bree, C. (Creator), Jansen, T. (Creator), Mathews, I. T. (Creator), Dao, K. (Creator), Najhawan, M. (Creator), Watrous, J. D. (Creator), Joosten, I. (Creator), Sharma, S. (Creator), Koenen, H. J. P. M. (Creator), Withoff, S. (Creator), Jonkers, I. (Creator), Netea-Maier, R. T. (Creator), Xavier, R. J. (Creator), Franke, L. (Creator), Xu, C.-J. (Creator), Joosten, L. A. B. (Creator), Sanna, S. (Creator), Jain, M. (Creator), Magadi Gopalaiah, V. K. (Creator), Clevers, H. (Creator), Wijmenga, C. (Creator), Netea, M. G. (Creator) & Li, Y. (Creator), figshare, 6-Jul-2021
DOI: 10.6084/m9.figshare.14920797, https://springernature.figshare.com/articles/dataset/Additional_file_12_of_Integration_of_metabolomics_genomics_and_immune_phenotypes_reveals_the_causal_roles_of_metabolites_in_disease/14920797
Dataset
Additional file 16 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
Chu, X. (Contributor), Jaeger, M. (Creator), Beumer, J. (Creator), Bakker, O. (Contributor), Aguirre-Gamboa, R. (Creator), Oosting, M. (Creator), Smeekens, S. P. (Creator), Moorlag, S. (Creator), Mourits, V. P. (Creator), Koeken, V. A. C. M. (Creator), de Bree, C. (Creator), Jansen, T. (Creator), Mathews, I. T. (Creator), Dao, K. (Creator), Najhawan, M. (Creator), Watrous, J. D. (Creator), Joosten, I. (Creator), Sharma, S. (Creator), Koenen, H. J. P. M. (Creator), Withoff, S. (Creator), Jonkers, I. (Contributor), Netea-Maier, R. T. (Creator), Xavier, R. J. (Creator), Franke, L. (Contributor), Xu, C.-J. (Creator), Joosten, L. A. B. (Creator), Sanna, S. (Contributor), Jain, M. (Creator), Magadi Gopalaiah, V. K. (Contributor), Clevers, H. (Creator), Wijmenga, C. (Contributor), Netea, M. G. (Creator) & Li, Y. (Creator), figshare, 7-Jul-2021
DOI: 10.6084/m9.figshare.14921197, https://springernature.figshare.com/articles/dataset/Additional_file_16_of_Integration_of_metabolomics_genomics_and_immune_phenotypes_reveals_the_causal_roles_of_metabolites_in_disease/14921197
Dataset

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ter Horst, R., Jaeger, M., Smeekens, S. P., Oosting, M., Swertz, M. A., Li, Y., Kumar, V., Diavatopoulos, D. A., Jansen, A. F. M., Lemmers, H., Toenhake-Dijkstra, H., van Herwaarden, A. E., Janssen, M., van der Molen, R. G., Joosten, I., Sweep, F. C. G. J., Smit, J. W., Netea-Maier, R. T., Koenders, M. M. J. F., ... Netea, M. G. (2016). Host and Environmental Factors Influencing Individual Human Cytokine Responses. Cell, 167(4), 1111-1124. https://doi.org/10.1016/j.cell.2016.10.018

@article{8189aad496a6421184d83c7ac1bc4b15,

title = "Host and Environmental Factors Influencing Individual Human Cytokine Responses",

abstract = "Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies.",

keywords = "C-REACTIVE PROTEIN, BODY-MASS INDEX, PROGESTERONE-RECEPTOR IMMUNOREACTIVITY, ORGAN-TRANSPLANT RECIPIENTS, MULTIPLE-SCLEROSIS, IMMUNE-SYSTEM, ORAL-CONTRACEPTIVES, GENDER-DIFFERENCES, DIABETES-MELLITUS, SERUM-LEVELS",

author = "{ter Horst}, Rob and Martin Jaeger and Smeekens, {Sanne P.} and Marije Oosting and Swertz, {Morris A.} and Yang Li and Vinod Kumar and Diavatopoulos, {Dimitri A.} and Jansen, {Anne F. M.} and Heidi Lemmers and Helga Toenhake-Dijkstra and {van Herwaarden}, {Antonius E.} and Matthijs Janssen and {van der Molen}, {Renate G.} and Irma Joosten and Sweep, {Fred C. G. J.} and Smit, {Johannes W.} and Netea-Maier, {Romana T.} and Koenders, {Mieke M. J. F.} and Xavier, {Ramnik J.} and {van der Meer}, {Jos W. M.} and Dinarello, {Charles A.} and Norman Pavelka and Cisca Wijmenga and Notebaart, {Richard A.} and Joosten, {Leo A. B.} and Netea, {Mihai G.}",

year = "2016",

month = nov,

day = "3",

doi = "10.1016/j.cell.2016.10.018",

language = "English",

volume = "167",

pages = "1111--1124",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

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ter Horst, R, Jaeger, M, Smeekens, SP, Oosting, M, Swertz, MA, Li, Y, Kumar, V, Diavatopoulos, DA, Jansen, AFM, Lemmers, H, Toenhake-Dijkstra, H, van Herwaarden, AE, Janssen, M, van der Molen, RG, Joosten, I, Sweep, FCGJ, Smit, JW, Netea-Maier, RT, Koenders, MMJF, Xavier, RJ, van der Meer, JWM, Dinarello, CA, Pavelka, N, Wijmenga, C, Notebaart, RA, Joosten, LAB & Netea, MG 2016, 'Host and Environmental Factors Influencing Individual Human Cytokine Responses', Cell, vol. 167, no. 4, pp. 1111-1124. https://doi.org/10.1016/j.cell.2016.10.018

TY - JOUR

T1 - Host and Environmental Factors Influencing Individual Human Cytokine Responses

AU - ter Horst, Rob

AU - Jaeger, Martin

AU - Smeekens, Sanne P.

AU - Oosting, Marije

AU - Swertz, Morris A.

AU - Li, Yang

AU - Kumar, Vinod

AU - Diavatopoulos, Dimitri A.

AU - Jansen, Anne F. M.

AU - Lemmers, Heidi

AU - Toenhake-Dijkstra, Helga

AU - van Herwaarden, Antonius E.

AU - Janssen, Matthijs

AU - van der Molen, Renate G.

AU - Joosten, Irma

AU - Sweep, Fred C. G. J.

AU - Smit, Johannes W.

AU - Netea-Maier, Romana T.

AU - Koenders, Mieke M. J. F.

AU - Xavier, Ramnik J.

AU - van der Meer, Jos W. M.

AU - Dinarello, Charles A.

AU - Pavelka, Norman

AU - Wijmenga, Cisca

AU - Notebaart, Richard A.

AU - Joosten, Leo A. B.

AU - Netea, Mihai G.

PY - 2016/11/3

Y1 - 2016/11/3

N2 - Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies.

AB - Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies.

KW - C-REACTIVE PROTEIN

KW - BODY-MASS INDEX

KW - PROGESTERONE-RECEPTOR IMMUNOREACTIVITY

KW - ORGAN-TRANSPLANT RECIPIENTS

KW - MULTIPLE-SCLEROSIS

KW - IMMUNE-SYSTEM

KW - ORAL-CONTRACEPTIVES

KW - GENDER-DIFFERENCES

KW - DIABETES-MELLITUS

KW - SERUM-LEVELS

U2 - 10.1016/j.cell.2016.10.018

DO - 10.1016/j.cell.2016.10.018

M3 - Article

SN - 0092-8674

VL - 167

SP - 1111

EP - 1124

JO - Cell

JF - Cell

IS - 4

ER -

Host and Environmental Factors Influencing Individual Human Cytokine Responses

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Keywords

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Additional file 22 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Additional file 12 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Additional file 16 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

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