Development and Functions of Antigen-Presenting Cells
Our body is equipped with an elegant and powerful immune system that, when properly directed, can help defeat currently incurable diseases. We study how the immune system functions with the goal of developing innovative medicines.
It has long been established that T cell-mediated immunity plays a vital role in protecting the body from infectious diseases and cancer. Yet we still have not developed effective strategies for inducing potent T cell responses.
Our study will focus on the biology of Antigen-Presenting Cells (APCs), due to their indispensable roles in regulating T cell-mediated immunity. Our goal is to contribute new ideas to the development of T cell-inducing vaccines and immunotherapies.
Current areas of interest
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Antigen-Presenting Cells comprise a heterogeneous group of cells, whose development is governed by interconnected gene regulatory networks. Among APCs, cDC1 have been proved to play nonredundant functions in initiating anti-viral and anti-tumor T cell responses, making them the most promising therapeutic target for developing cancer vaccine. One main obstacle that hinders DC-based cancer vaccine development is the incomplete understanding of cDC1 development, and the unavailability of cDC1. To overcome this challenge, we are characterizing the transcription factors, cis-regulatory elements, and environmental signals (in bone marrow and peripheral tissues) that regulate cDC1 lineage specification.
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The identification of transcription factors governing cDC1 development and studies using cDC1-depletion mouse models highlighted the nonredundant functions of cDC1 in initiating anti-tumor T cell responses, but the unique functions of cDC2 and monocyte-derived DC are less well understood. We recently identified the transcription factors that regulate cDC2 and monocyte development, and developed the first cDC2-depletion mouse model. We are characterizing the overlapping and unique functions of the main APC subsets using these new animal models.
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Our knowledge of steady-state APC development has grown rapidly, but whether their development and functions are dysregulated under disease conditions, and whether APC dysregulation contributes to the non-responsiveness to existing medicines remain unclear. We recently demonstrated cDC1 development is suppressed under chronic inflammatory conditions. We are characterizing the various stages of APC development in mouse cancer models, and investigating whether APC dysregulation contributes to the resistance to checkpoint blockade immunotherapies.