RESUMO
Regulated glycosylation controls T cell processes, including activation, differentiation and homing by creating or masking ligands for endogenous lectins. Here we show that stimuli promoting T helper type 1 (TH1), TH2 or interleukin 17-producing T helper (TH-17) differentiation can differentially regulate the glycosylation pattern of T helper cells and modulate their susceptibility to galectin-1, a glycan-binding protein with anti-inflammatory activity. Although TH1- and TH-17-differentiated cells expressed the repertoire of cell surface glycans critical for galectin-1-induced cell death, TH2 cells were protected from galectin-1 through differential sialylation of cell surface glycoproteins. Consistent with those findings, galectin-1-deficient mice developed greater TH1 and TH-17 responses and enhanced susceptibility to autoimmune neuroinflammation. Our findings identify a molecular link among differential glycosylation of T helper cells, susceptibility to cell death and termination of the inflammatory response.
Assuntos
Apoptose/imunologia , Galectina 1/imunologia , Inflamação/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Transferência Adotiva , Animais , Diferenciação Celular/imunologia , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Citometria de Fluxo , Galectina 1/genética , Galectina 1/metabolismo , Glicosilação , Humanos , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Inflamação/metabolismo , Interleucina-17/metabolismo , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Polissacarídeos/imunologia , Polissacarídeos/metabolismo , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/patologia , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/patologia , Células Th1/citologia , Células Th1/metabolismo , Células Th1/patologia , Células Th2/citologia , Células Th2/metabolismo , Células Th2/patologiaRESUMO
Recent evidence has implicated galectins and their ligands as master regulators of immune cell homeostasis. Whereas some members of this family, such as galectin-3, behave as amplifiers of the inflammatory cascade, others, such as galectin-1, trigger homeostatic signals to shut off T-cell effector functions. These carbohydrate-binding proteins, identified by shared consensus amino acid sequences and affinity for beta-galactoside-containing sugars, participate in the homeostasis of the inflammatory response, either by regulating cell survival and signaling, influencing cell growth and chemotaxis, interfering with cytokine secretion, mediating cell-cell and cell-matrix interactions or influencing tumor progression and metastasis. The current wealth of new information promises a future scenario in which individual members of the galectin family or their ligands will be used as powerful anti-inflammatory mediators and selective modulators of the immune response.