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CD226 promotes positive signals, whereas TIGIT transmits negative signals, forming a route comparable to the CD28/CTLA-4 signaling pathway ( In a variety of autoimmune and inflammatory diseases, VISTA, a novel negative checkpoint receptor, functions as a negative immune regulator, thereby preventing excessive immune activation ( + and IL17A + producing CD4 + T cells in the central nervous system (CNS), exhibiting an activation of T cell-mediated immunity and loss of peripheral tolerance, thus increasing the susceptibility to EAE ( 4.2 Challenges There are major obstacles to the therapeutic promise of next-generation checkpoint agonists

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