Next Article in Journal
Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study
Previous Article in Journal
Oxidative Stress at Birth Is Associated with the Concentration of Iron and Copper in Maternal Serum
Previous Article in Special Issue
Preconditioning with Short-Term Dietary Restriction Attenuates Cardiac Oxidative Stress and Hypertrophy Induced by Chronic Pressure Overload
Due to scheduled maintenance work on our core network, there may be short service disruptions on this website between 16:00 and 16:30 CEST on September 25th.
Article

Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness

1
Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
2
Bioinformatics and Computational Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
3
Determinants of Obesity and Cardiovascular Risk, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
4
Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
5
Center of Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
6
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
7
National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Thomas Roeder
Nutrients 2021, 13(5), 1492; https://doi.org/10.3390/nu13051492
Received: 29 March 2021 / Revised: 22 April 2021 / Accepted: 26 April 2021 / Published: 28 April 2021
(This article belongs to the Special Issue Dietary Restriction and Lifespan)
Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects’ blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4+ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4+ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4+ T cell immune responsiveness. View Full-Text
Keywords: fasting; refeeding; CD4+ T cell activation; SOMAscan; IGFBP1; PYY; IL1RL1; MFGE8; integrative bioinformatics fasting; refeeding; CD4+ T cell activation; SOMAscan; IGFBP1; PYY; IL1RL1; MFGE8; integrative bioinformatics
Show Figures

Figure 1

MDPI and ACS Style

Han, K.; Singh, K.; Rodman, M.J.; Hassanzadeh, S.; Baumer, Y.; Huffstutler, R.D.; Chen, J.; Candia, J.; Cheung, F.; Stagliano, K.E.R.; Pirooznia, M.; Powell-Wiley, T.M.; Sack, M.N. Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness. Nutrients 2021, 13, 1492. https://doi.org/10.3390/nu13051492

AMA Style

Han K, Singh K, Rodman MJ, Hassanzadeh S, Baumer Y, Huffstutler RD, Chen J, Candia J, Cheung F, Stagliano KER, Pirooznia M, Powell-Wiley TM, Sack MN. Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness. Nutrients. 2021; 13(5):1492. https://doi.org/10.3390/nu13051492

Chicago/Turabian Style

Han, Kim, Komudi Singh, Matthew J. Rodman, Shahin Hassanzadeh, Yvonne Baumer, Rebecca D. Huffstutler, Jinguo Chen, Julián Candia, Foo Cheung, Katherine E.R. Stagliano, Mehdi Pirooznia, Tiffany M. Powell-Wiley, and Michael N. Sack 2021. "Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness" Nutrients 13, no. 5: 1492. https://doi.org/10.3390/nu13051492

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop