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Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice
In response to external stimuli during immune responses, monocytes can have multifaceted roles such as pathogen clearance and tissue repair. However, aberrant control of monocyte activation can result in chronic inflammation and subsequent tissue damage. Granulocyte-macrophage colony-stimulating fac...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157487/ https://www.ncbi.nlm.nih.gov/pubmed/37153611 http://dx.doi.org/10.3389/fimmu.2023.1117828 |
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author | Monaghan, Kelly L. Zheng, Wen Akhter, Halima Wang, Lei Ammer, Amanda G. Li, Peng Lin, Jian-Xin Hu, Gangqing Leonard, Warren J. Wan, Edwin C. K. |
author_facet | Monaghan, Kelly L. Zheng, Wen Akhter, Halima Wang, Lei Ammer, Amanda G. Li, Peng Lin, Jian-Xin Hu, Gangqing Leonard, Warren J. Wan, Edwin C. K. |
author_sort | Monaghan, Kelly L. |
collection | PubMed |
description | In response to external stimuli during immune responses, monocytes can have multifaceted roles such as pathogen clearance and tissue repair. However, aberrant control of monocyte activation can result in chronic inflammation and subsequent tissue damage. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces monocyte differentiation into a heterogenous population of monocyte-derived dendritic cells (moDCs) and macrophages. However, the downstream molecular signals that dictate the differentiation of monocytes under pathological conditions is incompletely understood. We report here that the GM-CSF-induced STAT5 tetramerization is a critical determinate of monocyte fate and function. Monocytes require STAT5 tetramers to differentiate into moDCs. Conversely, the absence of STAT5 tetramers results in a switch to a functionally distinct monocyte-derived macrophage population. In the dextran sulfate sodium (DSS) model of colitis, STAT5 tetramer-deficient monocytes exacerbate disease severity. Mechanistically, GM-CSF signaling in STAT5 tetramer-deficient monocytes results in the overexpression of arginase I and a reduction in nitric oxide synthesis following stimulation with lipopolysaccharide. Correspondingly, the inhibition of arginase I activity and sustained supplementation of nitric oxide ameliorates the worsened colitis in STAT5 tetramer-deficient mice. This study suggests that STAT5 tetramers protect against severe intestinal inflammation through the regulation of arginine metabolism. |
format | Online Article Text |
id | pubmed-10157487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101574872023-05-05 Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice Monaghan, Kelly L. Zheng, Wen Akhter, Halima Wang, Lei Ammer, Amanda G. Li, Peng Lin, Jian-Xin Hu, Gangqing Leonard, Warren J. Wan, Edwin C. K. Front Immunol Immunology In response to external stimuli during immune responses, monocytes can have multifaceted roles such as pathogen clearance and tissue repair. However, aberrant control of monocyte activation can result in chronic inflammation and subsequent tissue damage. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces monocyte differentiation into a heterogenous population of monocyte-derived dendritic cells (moDCs) and macrophages. However, the downstream molecular signals that dictate the differentiation of monocytes under pathological conditions is incompletely understood. We report here that the GM-CSF-induced STAT5 tetramerization is a critical determinate of monocyte fate and function. Monocytes require STAT5 tetramers to differentiate into moDCs. Conversely, the absence of STAT5 tetramers results in a switch to a functionally distinct monocyte-derived macrophage population. In the dextran sulfate sodium (DSS) model of colitis, STAT5 tetramer-deficient monocytes exacerbate disease severity. Mechanistically, GM-CSF signaling in STAT5 tetramer-deficient monocytes results in the overexpression of arginase I and a reduction in nitric oxide synthesis following stimulation with lipopolysaccharide. Correspondingly, the inhibition of arginase I activity and sustained supplementation of nitric oxide ameliorates the worsened colitis in STAT5 tetramer-deficient mice. This study suggests that STAT5 tetramers protect against severe intestinal inflammation through the regulation of arginine metabolism. Frontiers Media S.A. 2023-04-20 /pmc/articles/PMC10157487/ /pubmed/37153611 http://dx.doi.org/10.3389/fimmu.2023.1117828 Text en Copyright © 2023 Monaghan, Zheng, Akhter, Wang, Ammer, Li, Lin, Hu, Leonard and Wan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Monaghan, Kelly L. Zheng, Wen Akhter, Halima Wang, Lei Ammer, Amanda G. Li, Peng Lin, Jian-Xin Hu, Gangqing Leonard, Warren J. Wan, Edwin C. K. Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice |
title | Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice |
title_full | Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice |
title_fullStr | Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice |
title_full_unstemmed | Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice |
title_short | Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice |
title_sort | tetramerization of stat5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157487/ https://www.ncbi.nlm.nih.gov/pubmed/37153611 http://dx.doi.org/10.3389/fimmu.2023.1117828 |
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