The Circadian Clock Controls Immune Checkpoint Pathway in Sepsis.

ABSTRACT: Sepsis and septic shock are associated with life-threatening organ dysfunction caused by an impaired host response to infections. Although circadian clock disturbance impairs the early inflammatory response, its impact on post-septic immunosuppression remains poorly elucidated. Here, we show that Bmal1, a core circadian clock gene, plays a role in the regulation of host immune responses in experimental sepsis. Mechanistically, Bmal1 deficiency in macrophages increases PKM2 expression and lactate production, which is required for expression of the immune checkpoint protein PD-L1 in a STAT1-dependent manner. Consequently, targeted ablation of Pkm2 in myeloid cells or administration of anti-PD-L1-neutralizing antibody or supplementation with recombinant interleukin-7 (IL-7) facilitates microb

SUBMITTER: Deng W 

PROVIDER: S-EPMC6094382 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature