| First Author | Collazo MM | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 7 | Pages | 1785-95 |
| PubMed ID | 22535653 | Mgi Jnum | J:187777 |
| Mgi Id | MGI:5438179 | Doi | 10.1002/eji.201142092 |
| Citation | Collazo MM, et al. (2012) Lineage extrinsic and intrinsic control of immunoregulatory cell numbers by SHIP. Eur J Immunol 42(7):1785-95 |
| abstractText | We previously showed that germline or induced SHIP deficiency expands immuno-regulatory cell numbers in T lymphoid and myeloid lineages. We postulated these increases could be interrelated. Here, we show that myeloid-specific ablation of SHIP leads to the expansion of both myeloid-derived suppressor cell (MDSC) and regulatory T (Treg) cell numbers, indicating SHIP-dependent control of Treg-cell numbers by a myeloid cell type. Conversely, T-lineage specific ablation of SHIP leads to expansion of Treg-cell numbers, but not expansion of the MDSC compartment, indicating SHIP also has a lineage intrinsic role in limiting Treg-cell numbers. However, the SHIP-deficient myeloid cell that promotes MDSC and Treg-cell expansion is not an MDSC as they lack SHIP protein expression. Thus, regulation of MDSC numbers in vivo must be controlled in a cell-extrinsic fashion by another myeloid cell type. We had previously shown that G-CSF levels are profoundly increased in SHIP(-/-) mice, suggesting this myelopoietic growth factor could promote MDSC expansion in a cell-extrinsic fashion. Consistent with this hypothesis, we find that G-CSF is required for expansion of the MDSC splenic compartment in mice rendered SHIP-deficient as adults. Thus, SHIP controls MDSC numbers, in part, by limiting production of the myelopoietic growth factor G-CSF. |
