No abstract

Key Points A trimeric extracellular moiety of APRIL has enhanced binding to BCMA and TACI compared with monomeric APRIL when incorporated into a CAR. T cells transduced with a trimeric APRIL-based CAR are a promising approach for the treatment of MM.

Highlights d CD8 + T cell function and survival is impaired in HSAN-I patients with SPTLC2 mutation d Mouse CD8 + T cells require SPTLC2 to protect against viral infections d SPTLC2-mediated sphingolipid synthesis prevents mTORC1 hyperactivation and cell death d Sphingolipid supplementation restores SPTLC2-deficient CD8 + T cell effector function

BackgroundSystemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease involving multiple organs. It is currently accepted that several genetic, environmental, and hormonal factors are contributing to its development. Innate immunity may have a great influence in autoimmunity through Toll-like receptors. TLR-7 recognizing single-strand RNA has been involved in SLE. Its activation induces intracellular signal with attraction of MyD88 and NF-kBp65, leading to IFN-α synthesis which correlate with disease activity.ObjectiveTo assess the expression of TLR-7, MyD88, and NF-kBp65 in B lymphocytes of Mayan women with SLE.MethodsOne hundred patients with SLE and 100 healthy controls, all of them Mayan women, were included. TLR-7 was analyzed on B and T lymphocytes, and MyD88 and NF-kB only in B lymphocytes. Serum INF-α level was evaluated by ELISA.ResultsSignificant expression (p < 0.0001) of TLR-7 in B and T lymphocytes and serum IFN-α increased (p = 0.034) was observed in patients. MyD88 and NF-kBp65 were also increased in B lymphocytes of patients. TLR-7 and NF-kBp65 expression correlated, but no correlation with INF-α and disease activity was detected.ConclusionData support the role of TLR-7 and signal proteins in the pathogenesis of SLE in the Mayan population of Yucatán.