| First Author | Rojo JM | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 16 | PubMed ID | 34445401 |
| Mgi Jnum | J:339392 | Mgi Id | MGI:6762267 |
| Doi | 10.3390/ijms22168698 | Citation | Rojo JM, et al. (2021) PI3-Kinase p110alpha Deficiency Modulates T Cell Homeostasis and Function and Attenuates Experimental Allergic Encephalitis in Mature Mice. Int J Mol Sci 22(16) |
| abstractText | Class I phosphoinositide 3-kinases (PI3K) are involved in the development of normal and autoimmune responses, including Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for human multiple sclerosis (MS). Here, the role of the ubiquitously expressed class IA PI3K p110alpha catalytic subunits in EAE has been analyzed using a model of Cre/flox mediated T cell specific deletion of p110alpha catalytic chain (p110alphaDeltaT). Comparison of two month-old (young) and six month-old (mature) p110alphaDeltaT mice and their wild type (WT) counterparts indicated loss of spleen CD4(+) T cells that increased with age, indicating a role of p110alpha in their homeostasis. In contrast, CD4(+) T regulatory (Treg) cells were enhanced in mature p110alphaDeltaT mice when compared to WT mice. Since Myelin Oligodendrocyte Glycoprotein (MOG) peptide-induced EAE is dependent on, or mediated by CD4(+) T cells and CD4(+) T cell-derived cytokines and controlled by Treg cells, development of EAE in young and mature WT or p110alphaDeltaT mice was analyzed. EAE clinical symptoms and disease scores in six month p110alphaDeltaT mice were significantly lower than those of mature WT, or young WT and p110alphaDeltaT mice. Furthermore, ex vivo antigen activation of lymph node cells from MOG immunized mature p110alphaDeltaT mice induced significantly lower levels of IFN-gamma and IL-17A than young p110alphaDeltaT or young and mature WT mice. Other cytokines including IL-2, IL-10 or TNF-alpha showed no significant differences between p110alphaDeltaT and WT mature mice. Our data show a lower incidence of MOG-induced EAE in mature p110alphaDeltaT mice linked to altered T cell homeostasis and lower secretion of inflammatory cytokines. |
