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 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.
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, China.
Jing
J
Zhang
Bing
B
Wang
Wen
W
Zhang
Yao
Y
Wei
Zhen
Z
Bian
Chen-Yu
CY
Zhang
Limin
L
Li
Ke
K
Zen
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D015850:Interleukin-6; D019707:Receptors, Chemokine; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse