Dectin-1 signaling in neutrophils up-regulates PD-L1 and triggers ROS-mediated suppression of CD4+ T cells.
| Publication Type | Academic Article |
| Authors | Deerhake M, Cardakli E, Shinohara M |
| Journal | J Leukoc Biol |
| Volume | 112 |
| Issue | 6 |
| Pagination | 1413-1425 |
| Date Published | 09/08/2022 |
| ISSN | 1938-3673 |
| Keywords | Neutrophils, Encephalomyelitis, Autoimmune, Experimental |
| Abstract | 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. Summary sentence: Mechanisms by which Dectin-1 signaling in neutrophils promotes a cellular phenotype with T cell-suppressive properties. |
| DOI | 10.1002/JLB.3A0322-152RR |
| PubMed ID | 36073780 |
| PubMed Central ID | PMC9701158 |