Glycosylation-dependent interaction between CD69 and S100A8/S100A9 complex is required for regulatory T-cell differentiation

摘要: Cluster of differentiation (CD)69 is a leukocyte activation receptor involved in the maintenance immune homeostasis and positively selected activated regulatory T (Treg) cells, implicating its role during Treg-cell differentiation. By RNA interference, we show that CD69 not sufficient to support conversion CD4(+) naive cells into Treg whereas it does human peripheral blood mononuclear (hPBMCs) (P < 0.01), suggesting ligand-receptor interaction required for function. Using immunoprecipitation mass spectrometry, identified S100A8/S100A9 complex as natural ligand hPBMCs. specifically associates with confirmed by vitro binding competition assay, treatment peptide-N-glycosidase significantly abolishes such association. In agreement, glycomics analysis determines glycosylation site N-glycan composition CD69, terminal removal sialic acid from N-linked glycans reverses generation forkhead box P3-positive (23.21%; P 0.05). More specifically, showed CD69-S100A8/S100A9 association up-regulation suppressor cytokine signaling 3 resulting inhibited signal transducer activator transcription (36.54% increase upon silencing; 0.01). This might turn secretion key regulator TGF-β (∼ 3.28-fold decrease 0.05), leading reduced production IL-4 Our results demonstrate functional mechanistic interplays between supporting