| First Author | Zotes TM | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 8 | Pages | e72960 |
| PubMed ID | 24009720 | Mgi Jnum | J:206413 |
| Mgi Id | MGI:5550204 | Doi | 10.1371/journal.pone.0072960 |
| Citation | Zotes TM, et al. (2013) PI3K p110delta is expressed by gp38(-)CD31(+) and gp38(+)CD31(+) spleen stromal cells and regulates their CCL19, CCL21, and LTbetaR mRNA levels. PLoS One 8(8):e72960 |
| abstractText | The role of p110delta PI3K in lymphoid cells has been studied extensively, showing its importance in immune cell differentiation, activation and development. Altered T cell localization in p110delta-deficient mouse spleen suggested a role for p110delta in non-hematopoietic stromal cells, which maintain hematopoietic cell segregation. We tested this hypothesis using p110delta(WT/WT) mouse bone marrow to reconstitute lethally irradiated p110delta(WT/WT) or p110delta(D910A/D910A) (which express catalytically inactive p110delta) recipients, and studied localization, number and percentage of hematopoietic cell subsets in spleen and lymph nodes, in homeostatic conditions and after antigen stimulation. These analyses showed diffuse T cell areas in p110delta(D910A/D910A) and in reconstituted p110delta(D910A/D910A) mice in homeostatic conditions. In these mice, spleen CD4(+) and CD8(+) T cell numbers did not increase in response to antigen, suggesting that a p110delta(D910A/D910A) stroma defect impedes correct T cell response. FACS analysis of spleen stromal cell populations showed a decrease in the percentage of gp38(-)CD31(+) cells in p110delta(D910A/D910A) mice. qRT-PCR studies detected p110delta mRNA expression in p110delta(WT/WT) spleen gp38(-)CD31(+) and gp38(+)CD31(+) subsets, which was reduced in p110delta(D910A/D910A) spleen. Lack of p110delta activity in these cell populations correlated with lower LTbetaR, CCL19 and CCL21 mRNA levels; these molecules participate in T cell localization to specific spleen areas. Our results could explain the lower T cell numbers and more diffuse T cell areas found in p110delta(D910A/D910A) mouse spleen, as well as the lower T cell expansion after antigen stimulation in p110delta(D910A/D910A) compared with p110delta(WT/WT) mice. |
