Unknown

Dataset Information

0

Inhibitory affinity modulation of FcγRIIA ligand binding by glycosphingolipids by inside-out signaling.


ABSTRACT: The interaction of the human FcγRIIA with immune complexes (ICs) promotes neutrophil activation and thus must be tightly controlled to avoid damage to healthy tissue. Here, we demonstrate that a fungal-derived soluble β-1,3/1,6-glucan binds to the glycosphingolipid long-chain lactosylceramide (LacCer) to reduce FcγRIIA-mediated recruitment to immobilized ICs under flow, a process requiring high-affinity FcγRIIA-immunoglobulin G (IgG) interactions. The inhibition requires Lyn phosphorylation of SHP-1 phosphatase and the FcγRIIA immunotyrosine-activating motif. β-glucan reduces the effective 2D affinity of FcγRIIA for IgG via Lyn and SHP-1 and, in vivo, inhibits FcγRIIA-mediated neutrophil recruitment to intravascular IgG deposited in the kidney glomeruli in a glycosphingolipid- and Lyn-dependent manner. In contrast, β-glucan did not affect FcγR functions that bypass FcγR affinity for IgG. In summary, we have identified a pathway for modulating the 2D affinity of FcγRIIA for ligand that relies on LacCer-Lyn-SHP-1-mediated inhibitory signaling triggered by β-glucan, a previously described activator of innate immunity.

SUBMITTER: Okubo K 

PROVIDER: S-EPMC8218468 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC1219217 | biostudies-other
| S-EPMC3244936 | biostudies-literature
| S-EPMC7521114 | biostudies-literature
| S-EPMC5253313 | biostudies-literature
| S-EPMC3003088 | biostudies-literature
| S-EPMC5545807 | biostudies-literature
| S-EPMC7411472 | biostudies-literature
| S-EPMC3882713 | biostudies-literature
| S-EPMC2759756 | biostudies-literature
| S-EPMC3311051 | biostudies-literature