Genome-wide transcription profiling identifies the mechanisms of LFA-1 contributing to CD8+ T Cell Activation and immune signal network (50.26)

Abstract

Abstract Our previous data demonstrated that the function of LFA-1 is to enhance TCR signaling through the immunological synapse and deliver distinct signal in CD8+ T cell activation. However, the detailed molecular pathways that regulate these processes and global impact on immune functions are poorly defined. The purpose of this genomic study is to explore and understand the LFA-1 and TCR signaling network with CD8+ T cell transcription profiling. CD8+ T cells from C57BL/6 mice and LFA-1-KO mice before and after stimulation were applied to the Mouse Whole Genome Oligo Microarray. Statistic analysis identified a list of LFA-1-associated genes differentially expressed in activated LFA-1-KO CD8+ T cells. Pathway analysis indicated that most of these genes are enriched in IL-10 signaling/ p38 MAPK signaling/ cell cycle regulation/ notch signaling/ NK signaling/ chemokine signaling. Furthermore, biological function analysis implicated these genes enriched in the functions of antigen presentation/ cell-mediated immune response/ inflammatory response/ cellular development/ cell-to-cell signaling and interaction/ immune cell trafficking/ cellular growth and proliferation/ inflammatory disease/ lymphoid tissue structure and development. Our results indicated that LFA-1 plays an important role in the immune signal network and has a global impact on immune system, and provided a complete genome-wide database to further characterize the molecular mechanisms of LFA-1 during T cell activation.