Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response
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Program death-1 (PD-1) is a co-inhibitory receptor inducibly expressed on activated T cells. PD-1 has been reported to be associated with the development of several autoimmune diseases including rheumatoid arthritis, but the precise cellular and molecular mechanisms have not been fully elucidated. To study the role of PD-1 in the pathogenesis of rheumatoid arthritis and the possible underlying mechanisms, we performed collagen-induced arthritis (CIA) in C57BL/6 mice. Here, we show that PD-1 deficiency leads to the development of severe CIA in mice. When analyzing T cells from CIA mice ex vivo, we noticed aberrant antigen-specific Th17 responses in mice lacking PD-1. This is possibly due to deregulated activation of PKC-θ and Akt. In support of this notion, treating Pdcd1 −/− mice with an inhibitor of PI3-kinase that is upstream of PKC-θ and Akt significantly suppressed the disease severity. Therefore, our data indicate that PD-1 dampens antigen-specific Th17 response, thus inhibiting the disease.
KeywordsProgram death-1 Collagen-induced arthritis Th17 PI3-kinase Akt
This work was supported by the National Natural Science Foundation of China (NNSF 81201371, to L. Yang), Young Researcher Culturing Plan from Xiangya Hospital, Young Teacher Exploring Plan from Central South University (to L. Yang) and NIH R01 AR049775 and AI090901 (to J. Zhang).
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Conflict of interest
The authors declare no competing financial interests.
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