Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death.
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.
Toscano
Marta A
MA
División de Immunogenética. Hospital de Clínicas José de San Martín, Facultad de Medicina, Universidad de Buenos Aires, C1120AAF Buenos Aires, Argentina.
Bianco
Germán A
GA
Ilarregui
Juan M
JM
Croci
Diego O
DO
Correale
Jorge
J
Hernandez
Joseph D
JD
Zwirner
Norberto W
NW
Poirier
Francoise
F
Riley
Eleanor M
EM
Baum
Linda G
LG
Rabinovich
Gabriel A
GA
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D037483:Galectin 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011134:Polysaccharides / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology
D037483:Galectin 1; D020381:Interleukin-17; D008562:Membrane Glycoproteins; D011134:Polysaccharides