Sialylation may be dispensable for reciprocal modulation of helper T cells by intravenous immunoglobulin.
Several mechanisms account for the beneficial effect of intravenous immunoglobulin (IVIg) in autoimmune and inflammatory diseases. These mechanisms include effects on the cellular compartment and on the humoral compartment. Thus, IVIg impacts on dendritic cells, macrophages, neutrophils, basophils, NK cells, and B and T lymphocytes. Several studies have emphasized that the antiinflammatory effect of IVIg is dependent on α2,6-sialylation of the N-linked glycan on asparagine-297 of the Fc portion of IgG. However, recent reports have questioned the necessity of sialylated Fc and the role of FcγRIIB in IVIg-mediated antiinflammatory effects. In view of the critical role played by Th17 cells in several autoimmune pathologies and the increasing use of IVIg in several of these conditions, by using neuraminidase-treated, desialylated IVIg, we addressed whether the α2,6-sialylation of IgG is essential for the beneficial effect of IVIg in experimental autoimmune encephalomyelitis (EAE), a Th17-driven condition, and for the reciprocal modulation of helper T-cell subsets. We observed no difference in the ability of IVIg to ameliorate EAE irrespective of its sialylation. Our findings thus show that sialylation of IVIg is not necessary for IVIg-mediated amelioration of EAE or for downregulation of Th17 cells and upregulation of regulatory T cells.
Institut National de la Sante et de la Recherche Medicale Unité 1138, Paris, France; Centre de Recherche des Cordeliers, Equipe 16-Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie - Paris, Paris, France.
Shivashankar
S
Othy
Selma
S
Topçu
Chaitrali
C
Saha
Prathap
P
Kothapalli
Sebastien
S
Lacroix-Desmazes
Fabian
F
Käsermann
Sylvia
S
Miescher
Jagadeesh
J
Bayry
Srini V
SV
Kaveri
D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000209:etiology; D005260:Female; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000502:physiology
D007141:Immunoglobulin Fc Fragments; D016756:Immunoglobulins, Intravenous; D019158:N-Acetylneuraminic Acid
Experimental autoimmune encephalomyelitis; Intravenous immunoglobulin; Regulatory T cells; Sialylation; Th1; Th17