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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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