Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

Abstract

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.

• Authors: Jing Zhang, Bing Wang, Wen Zhang, Yao Wei, Zhen Bian, Chen-Yu Zhang, Limin Li, Ke Zen
• Journal: PloS one (PLoS One) Vol. 8 Issue 8 Pg. e70828 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23951017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD11b Antigen
• Gr-1 protein, mouse
• Interleukin-6
• Receptors, Chemokine
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Granulocyte-Macrophage Colony-Stimulating Factor
• Dextran Sulfate
• Jak2 protein, mouse
• Janus Kinase 2
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Ptpn1 protein, mouse

Topics

• Animals
• Bone Marrow (drug effects, immunology, pathology)
• CD11b Antigen (genetics, immunology)
• Cell Proliferation
• Colitis (chemically induced, genetics, immunology, pathology)
• Dextran Sulfate
• Gene Expression
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
• Interleukin-6 (pharmacology)
• Janus Kinase 2 (genetics, immunology)
• Leukocytes, Mononuclear (drug effects, immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Myeloid Cells (drug effects, immunology, pathology)
• Protein Tyrosine Phosphatase, Non-Receptor Type 1 (deficiency, genetics, immunology)
• Receptors, Chemokine (genetics, immunology)
• STAT3 Transcription Factor (genetics, immunology)
• Signal Transduction
• Spleen (drug effects, immunology, pathology)