Inhibition of Phosphoinositide 3-Kinase p110delta Does Not Affect T Cell Driven Development of Type 1 Diabetes Despite Significant Effects on Cytokine Production
| Autor: | Anne Cooke, Ariana Barbera Betancourt, Klaus Okkenhaug, Juliet L. Emery, Maja Wallberg, Asha Recino, F. Susan Wong |
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| Přispěvatelé: | Cooke, Anne [0000-0003-3327-6081], Okkenhaug, Klaus [0000-0002-9432-4051], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Adoptive cell transfer Class I Phosphatidylinositol 3-Kinases medicine.medical_treatment T cell Cellular differentiation T-Lymphocytes lcsh:Medicine chemical and pharmacologic phenomena Mice Transgenic Mice SCID Biology Pharmacology Diabetes Mellitus Experimental 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Immune system Mice Inbred NOD Internal medicine medicine Cytotoxic T cell Animals lcsh:Science Cells Cultured Phosphoinositide-3 Kinase Inhibitors Multidisciplinary Adenine lcsh:R FOXP3 Cell Differentiation 3. Good health Mice Inbred C57BL 030104 developmental biology Cytokine medicine.anatomical_structure Endocrinology Diabetes Mellitus Type 1 P110δ Mice Inbred CBA Quinazolines Cytokines lcsh:Q Female 030215 immunology Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 1, p e0146516 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Type 1 diabetes is caused by the destruction of insulin producing beta cells by the immune system. The p110δ isoform of PI3K is expressed primarily in cells of haematopoietic origin and the catalytic activity of p110δ is important for the activation of these cells. Targeting of this pathway offers an opportunity to reduce immune cell activity without unwanted side effects. We have explored the effects of a specific p110δ isoform inhibitor, IC87114, on diabetogenic T cells both in vitro and in vivo, and find that although pharmacological inhibition of p110δ has a considerable impact on the production of pro-inflammatory cytokines, it does not delay the onset of diabetes after adoptive transfer of diabetogenic cells. Further, we demonstrate that combination treatment with CTLA4-Ig does not improve the efficacy of treatment, but instead attenuates the protective effects seen with CTLA4-Ig treatment alone. Our results suggest that decreased IL-10 production by Foxp3+ CD4+ T cells in the presence of IC87114 negates individual anti-inflammatory effects of IC8114 and CTLA4-Ig. |
| Databáze: | OpenAIRE |
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