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Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4(+) T Cell Responsiveness
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146063/ https://www.ncbi.nlm.nih.gov/pubmed/33924911 http://dx.doi.org/10.3390/nu13051492 |
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author | Han, Kim Singh, Komudi Rodman, Matthew J. Hassanzadeh, Shahin Baumer, Yvonne Huffstutler, Rebecca D. Chen, Jinguo Candia, Julián Cheung, Foo Stagliano, Katherine E. R. Pirooznia, Mehdi Powell-Wiley, Tiffany M. Sack, Michael N. |
author_facet | Han, Kim Singh, Komudi Rodman, Matthew J. Hassanzadeh, Shahin Baumer, Yvonne Huffstutler, Rebecca D. Chen, Jinguo Candia, Julián Cheung, Foo Stagliano, Katherine E. R. Pirooznia, Mehdi Powell-Wiley, Tiffany M. Sack, Michael N. |
author_sort | Han, Kim |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8146063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81460632021-05-26 Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4(+) T Cell Responsiveness Han, Kim Singh, Komudi Rodman, Matthew J. Hassanzadeh, Shahin Baumer, Yvonne Huffstutler, Rebecca D. Chen, Jinguo Candia, Julián Cheung, Foo Stagliano, Katherine E. R. Pirooznia, Mehdi Powell-Wiley, Tiffany M. Sack, Michael N. Nutrients Article 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. MDPI 2021-04-28 /pmc/articles/PMC8146063/ /pubmed/33924911 http://dx.doi.org/10.3390/nu13051492 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Han, Kim Singh, Komudi Rodman, Matthew J. Hassanzadeh, Shahin Baumer, Yvonne Huffstutler, Rebecca D. Chen, Jinguo Candia, Julián Cheung, Foo Stagliano, Katherine E. R. Pirooznia, Mehdi Powell-Wiley, Tiffany M. Sack, Michael N. Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4(+) T Cell Responsiveness |
title | Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4(+) T Cell Responsiveness |
title_full | Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4(+) T Cell Responsiveness |
title_fullStr | Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4(+) T Cell Responsiveness |
title_full_unstemmed | Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4(+) T Cell Responsiveness |
title_short | Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4(+) T Cell Responsiveness |
title_sort | identification and validation of nutrient state-dependent serum protein mediators of human cd4(+) t cell responsiveness |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146063/ https://www.ncbi.nlm.nih.gov/pubmed/33924911 http://dx.doi.org/10.3390/nu13051492 |
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