LAUSR

Dectin‐1 is known to drive proinflammatory cytokine production by macrophages and dendritic cells which promotes Th17 CD4+ T cell responses in the setting of fungal infection. However, the role of Dectin‐1 signaling in neutrophils and its impact on CD4+ T cells is not well understood. In this study, we found that neutrophils stimulated with a Dectin‐1 agonist diminish CD4+ T cell viability in a rapid and reactive oxygen species (ROS)‐dependent manner. Furthermore, Dectin‐1 promoted neutrophil PD‐L1 expression via Syk and Card9 signaling, along with other immune‐checkpoint factors in a neutrophil‐biased manner. Although neutrophil PD‐L1 did not significantly impact disease severity in experimental autoimmune encephalomyelitis (EAE), we found that CNS‐infiltrated neutrophils potently up‐regulate PD‐L1 expression. Furthermore, a subset of PD‐L1+ neutrophils was also found to express MHC‐II during EAE. In summary, we found that Dectin‐1 elicits a biphasic neutrophil response in which (1) T‐cell suppressive ROS is followed by (2) up‐regulation of PD‐L1 expression. This response may serve to limit excess CD4+ T cell‐driven inflammation in infection or autoimmunity while preserving host‐defense functions of neutrophils.