Basic science on human T follicular helper cells
T follicular helper (Tfh) cells represent a CD4+ T cell subset that plays fundamental roles for antibody responses. Tfh cells are critical for the generation of antibody responses as well as for the establishment of long-lived and high-affinity B cell clones. During the past decade, my lab has identified multiple key factors and pathways associated with human Tfh cell differentiation. We have also identified phenotypically and functionally distinct subsets within human Tfh cells. Currently we are aiming at elucidating the role of a transcription factor highly expressed by human Tfh cells for Tfh differentiation and/or functions in humans. Also we are interested in how checkpoint molecules highly expressed by Tfh cells contribute to the biological features of human Tfh cells.
Tfh response after Flu vaccination
While both vaccination and infection induce Tfh and antibody response, the magnitude and the quality of Tfh responses are radically different. Our previous studies show that seasonal influenza vaccination induces antibody response by activating a specific Tfh subset, called Tfh1 cells, together with influenza-specific memory B cells in humans. We aim to define the fundamental biological differences on memory Tfh cells generated by influenza infection and vaccination, and determine the key molecules and pathways associated with long-lived memory Tfh cells in humans.
Pathogenic CD4+ T cells in human neuroinflammatory diseases
Depletion of B cells is effective to treat patients with neuromyelitis optica (NMO) and multiple sclerosis (MS), but the immune mechanism remains unclear. We are interested in how B cell depletion affects the antigen-specific CD4+ T cell repertoires in patients. Towards this goal, we are currently developing a new assay that permits the detection of antigen-specific T cells with superior sensitivity and specificity to currently available assays.
Pathogenic Tfh cells in Systemic Lupus Erythematosus
Tfh cells play a major pathogenic role in Systemic Lupus Erythematosus (SLE). However, the precise mechanism remains largely obscure. We are aiming at identifying the feature of pathogenic Tfh cells unique to SLE, and determining how the pathogenic Tfh cells contribute to altered B cell responses in patients with SLE.