Lamtor1 Regulates The Proliferation And Activation Of Peripheral T Cell

T lymphocytes are the main cells that exert antigen-specific immunity.They can secrete cytokines,assist the germinal center reaction with B cells and directly kill tar-get cells.They play important roles in immune regulation and immune memory,and are critical in both humoral immunity and cellular immunity.T cells develop in the thymus,migrate to the periphery,interact with antigen presenting cells(APCs)and then proliferate and activate,and differentiate into different T cell subsets.The prolif-eration,activation and differentiation of T lymphocytes are the key to promoting and inhibiting the function of immune cells.Studying the molecular mechanisms of T cell proliferation and activation will help provide new immunotherapeutic targets.The current researches on T cells are not limited to the field of immunology.Many metabolic-related molecules and signaling pathways have been shown to play an important role in T cells.Ragulator complex,which is consisted of Lamtorl-Lamtor5,switch anabolism and catabolism located on the lysosomal mem-brane by regulating the mTORC1 and AMPK signaling pathways.We focuse on the role of Lamtorl in T cells.The innovation in this thesis is that mixed bone marrow(BM)chimera mice reconstituted with Lamtorfl/flCD4Cre and wild-type BM were used to study the role of Lamtorl in T cell development,activation and differentiation.The results showed that the deletion of Lamtorl in T cell did not affect T cell devel-opment.Reduced phosphorylation of ERK1/2 and S6 seemed accounting for the de-creasing of T cell numbers in peripheral and T cell activation and proliferation.Inhi-bition of T cell activation appeared to reduce TFH cell differentiation.In summary,Lamtorl may mediate mTORC1 and MAPK signaling pathways to regulate T cell proliferation and activation.The Ragulator complex provides an an-chor site for mTORC1 on the lysosomal membrane,and Lamtor2/Lamtor3 form a subcomplex that provides an anchor site for MEK1.Lamtorl is critical to maintain the stability of these two complexes.Once Lamtorl is deleted,the phosphorylation of mTOCR1 and MEK1 are inhibited,and suppress the proliferation and activation of T cells.