PI3K p110δ is expressed by gp38(-)CD31(+) and gp38(+)CD31(+) spleen stromal cells and regulates their CCL19, CCL21, and LTβR mRNA levels
| Autor: | Carlos Oscar S. Sorzano, Ana C. Carrera, Domingo F. Barber, Klaus Okkenhaug, Teresa M. Zotes, Roberto Spada, Vladimir Mulens, Sonia Pérez-Yagüe |
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| Přispěvatelé: | Okkenhaug, Klaus [0000-0002-9432-4051], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
Stromal cell
Lymphoid Tissue T cell Science Cell Spleen Biology Immunophenotyping Mice Antigen Lymphotoxin beta Receptor T-Lymphocyte Subsets medicine Animals RNA Messenger Antigens Antigen-presenting cell Mice Knockout Multidisciplinary Membrane Glycoproteins Chemokine CCL21 CCL19 Molecular biology Class Ia Phosphatidylinositol 3-Kinase Platelet Endothelial Cell Adhesion Molecule-1 medicine.anatomical_structure Gene Expression Regulation Immunology Tumor Necrosis Factors Medicine Chemokine CCL19 Stromal Cells CD8 Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 8, p e72960 (2013) |
| DOI: | 10.17863/cam.24915 |
| Popis: | The role of p110δ PI3K in lymphoid cells has been studied extensively, showing its importance in immune cell differentiation, activation and development. Altered T cell localization in p110δ-deficient mouse spleen suggested a role for p110δ in non-hematopoietic stromal cells, which maintain hematopoietic cell segregation. We tested this hypothesis using p110δ(WT/WT) mouse bone marrow to reconstitute lethally irradiated p110δ(WT/WT) or p110δ(D910A/D910A) (which express catalytically inactive p110δ) 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 p110δ(D910A/D910A) and in reconstituted p110δ(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 p110δ(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 p110δ(D910A/D910A) mice. qRT-PCR studies detected p110δ mRNA expression in p110δ(WT/WT) spleen gp38(-)CD31(+) and gp38(+)CD31(+) subsets, which was reduced in p110δ(D910A/D910A) spleen. Lack of p110δ activity in these cell populations correlated with lower LTβR, 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 p110δ(D910A/D910A) mouse spleen, as well as the lower T cell expansion after antigen stimulation in p110δ(D910A/D910A) compared with p110δ(WT/WT) mice. |
| Databáze: | OpenAIRE |
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