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Histidine decarboxylase (HDC)-expressing granulocytic myeloid cells induce and recruit Foxp3+regulatory T cells in murine colon cancer
- Source :
- OncoImmunology; March 2017, Vol. 6 Issue: 3
- Publication Year :
- 2017
-
Abstract
- ABSTRACTThe colorectal tumor microenvironment contains a diverse population of myeloid cells that are recruited and converted to immunosuppressive cells, thus facilitating tumor escape from immunoediting. We have identified a genetically and functionally distinct subset of dynamic bone marrow myeloid cells that are characterized by histidine decarboxylase (HDC) expression. Lineage tracing in Hdc-CreERT2;R26-LSL-tdTomato mice revealed that in homeostasis, there is a strong bias by HDC+myeloid cells toward the CD11b+Ly6Ghigranulocytic lineage, which was accelerated during azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic carcinogenesis. More importantly, HDC+myeloid cells strongly promoted colonic tumorigenesis, and colon tumor progression was profoundly suppressed by diphtheria toxin A (DTA)-mediated depletion of HDC+granulocytic myeloid cells. In addition, tumor infiltration by Foxp3+regulatory T cells (Tregs) was markedly impaired following HDC+myeloid cell depletion. We identified an HDC+myeloid-derived Cxcl13/Cxcr5 axis that mediated Foxp3 expression and Treg proliferation. Ablation of HDC+myeloid cells or disruption of the Cxcl13/Cxcr5 axis by gene knockdown impaired the production and recruitment of Tregs. Cxcl13 induction of Foxp3 expression in Tregs during tumorigenesis was associated with Stat3 phosphorylation. Overall, HDC+granulocytic myeloid cells affect CD8+T cells directly and indirectly through the modulation of Tregs and thus appear to play key roles in suppressing tumoricidal immunity.
Details
- Language :
- English
- ISSN :
- 21624011 and 2162402X
- Volume :
- 6
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- OncoImmunology
- Publication Type :
- Periodical
- Accession number :
- ejs41626795
- Full Text :
- https://doi.org/10.1080/2162402X.2017.1290034