| First Author | Montes-Casado M | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 12 | PubMed ID | 34203838 |
| Mgi Jnum | J:339390 | Mgi Id | MGI:6751160 |
| Doi | 10.3390/ijms22126405 | Citation | Montes-Casado M, et al. (2021) The PI-3-Kinase P110alpha Catalytic Subunit of T Lymphocytes Modulates Collagen-Induced Arthritis. Int J Mol Sci 22(12) |
| abstractText | The phosphatidylinositol 3-kinase (PI3K) family of enzymes plays a determinant role in inflammation and autoimmune responses. However, the implication of the different isoforms of catalytic subunits in these processes is not clear. Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that entails innate and adaptive immune response elements in which PI3K is a potential hub for immune modulation. In a mouse transgenic model with T-cell-specific deletion of p110alpha catalytic chain (p110alpha(-/-)DeltaT), we show the modulation of collagen-induced arthritis (CIA) by this isoform of PI3K. In established arthritis, p110alpha(-/-)DeltaT mice show decreased prevalence of illness than their control siblings, higher IgG1 titers and lower levels of IL-6 in serum, together with decreased ex vivo Collagen II (CII)-induced proliferation, IL-17A secretion and proportion of naive T cells in the lymph nodes. In a pre-arthritis phase, at 13 days post-Ag, T-cell-specific deletion of p110alpha chain induced an increased, less pathogenic IgG1/IgG2a antibodies ratio; changes in the fraction of naive and effector CD4(+) subpopulations; and an increased number of CXCR5(+) T cells in the draining lymph nodes of the p110alpha(-/-)DeltaT mice. Strikingly, T-cell blasts in vitro obtained from non-immunized p110alpha(-/-)DeltaT mice showed an increased expression of CXCR5, CD44 and ICOS surface markers and defective ICOS-induced signaling towards Akt phosphorylation. These results, plus the accumulation of cells in the lymph nodes in the early phase of the process, could explain the diminished illness incidence and prevalence in the p110alpha(-/-)DeltaT mice and suggests a modulation of CIA by the p110alpha catalytic chain of PI3K, opening new avenues of intervention in T-cell-directed therapies to autoimmune diseases. |
