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Protein Tyrosine Phosphatase 1B Deficiency Ameliorates Murine Experimental Colitis via the Expansion of Myeloid-Derived Suppressor Cells

Protein tyrosine phosphatase 1B (PTP1B) is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS)-induced murine exper...

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Autores principales: Zhang, Jing, Wang, Bing, Zhang, Wen, Wei, Yao, Bian, Zhen, Zhang, Chen-Yu, Li, Limin, Zen, Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739765/
https://www.ncbi.nlm.nih.gov/pubmed/23951017
http://dx.doi.org/10.1371/journal.pone.0070828
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author Zhang, Jing
Wang, Bing
Zhang, Wen
Wei, Yao
Bian, Zhen
Zhang, Chen-Yu
Li, Limin
Zen, Ke
author_facet Zhang, Jing
Wang, Bing
Zhang, Wen
Wei, Yao
Bian, Zhen
Zhang, Chen-Yu
Li, Limin
Zen, Ke
author_sort Zhang, Jing
collection PubMed
description Protein tyrosine phosphatase 1B (PTP1B) is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS)-induced murine experimental colitis via expanding CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM), peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.
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spelling pubmed-37397652013-08-15 Protein Tyrosine Phosphatase 1B Deficiency Ameliorates Murine Experimental Colitis via the Expansion of Myeloid-Derived Suppressor Cells Zhang, Jing Wang, Bing Zhang, Wen Wei, Yao Bian, Zhen Zhang, Chen-Yu Li, Limin Zen, Ke PLoS One Research Article Protein tyrosine phosphatase 1B (PTP1B) is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS)-induced murine experimental colitis via expanding CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM), peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs. Public Library of Science 2013-08-09 /pmc/articles/PMC3739765/ /pubmed/23951017 http://dx.doi.org/10.1371/journal.pone.0070828 Text en © 2013 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Jing
Wang, Bing
Zhang, Wen
Wei, Yao
Bian, Zhen
Zhang, Chen-Yu
Li, Limin
Zen, Ke
Protein Tyrosine Phosphatase 1B Deficiency Ameliorates Murine Experimental Colitis via the Expansion of Myeloid-Derived Suppressor Cells
title Protein Tyrosine Phosphatase 1B Deficiency Ameliorates Murine Experimental Colitis via the Expansion of Myeloid-Derived Suppressor Cells
title_full Protein Tyrosine Phosphatase 1B Deficiency Ameliorates Murine Experimental Colitis via the Expansion of Myeloid-Derived Suppressor Cells
title_fullStr Protein Tyrosine Phosphatase 1B Deficiency Ameliorates Murine Experimental Colitis via the Expansion of Myeloid-Derived Suppressor Cells
title_full_unstemmed Protein Tyrosine Phosphatase 1B Deficiency Ameliorates Murine Experimental Colitis via the Expansion of Myeloid-Derived Suppressor Cells
title_short Protein Tyrosine Phosphatase 1B Deficiency Ameliorates Murine Experimental Colitis via the Expansion of Myeloid-Derived Suppressor Cells
title_sort protein tyrosine phosphatase 1b deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739765/
https://www.ncbi.nlm.nih.gov/pubmed/23951017
http://dx.doi.org/10.1371/journal.pone.0070828
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