Reprogramming of myeloid compartments supporting tissue repair during DSS-induced colitis recovery
| Autor: | Alexandra V Tremblay, Zhen Bian, Shuo Niu, Courtney Culpepper, Yuan Liu |
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| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 196:188.15-188.15 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.196.supp.188.15 |
| Popis: | Myeloid-derived suppressor cells (MDSC) emerging during tumor growth or chronic inflammation play a critical role in regulating T cell function. However, mechanisms governing the generation of these cells remain unclear and need to be further defined. Using a DSS-induced colitis and recovery model, we characterized the dynamic changes within the myeloid compartments and the emerging of MDSC during active and resolution phases of inflammation. We show that the immature myeloid cell population expands and undergoes a functional reprogramming event in bone marrow (BM) and the spleen to form suppressive MDSC not at the active inflammation phase, but specifically at the resolution phase during colitis transition to recovery. In particular, two major functional changes occur when colitic mice were allowed to recover: 1) CD11b+Gr-1+myeloid cells in bone marrow and spleen acquire T cell suppressive functions, and 2) immature granulocytic myeloid cells increase the expression of chemokine receptor CXCR2, which enables their entry into circulation from BM. Additionally we determined enhanced activation of STAT3 and subsequent transcriptional enhancement of Arg1, iNOS, and gp91 in the MDSC isolated from resolution time points. We found that IL-17, the major cytokine associated with active colitis, remains elevated in the serum throughout the wound healing/resolution process. IL-17, together with the enhanced production of tissue repair cytokines, including IL-10, an activator of STAT3, produce a unique cytokine profile, resulting in a switch to induce reprograming and mobilization of the immature myeloid cells to suppress the inflammatory reaction in favor of tissue repair. |
| Databáze: | OpenAIRE |
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