Requirement for leptin in the induction and progression of autoimmune encephalomyelitis.
Recent evidence indicates that leptin modifies T cell immunity, and may provide a key link between nutritional deficiency and immune dysfunction. To study the influence of leptin on autoimmunity, susceptibility to experimental autoimmune encephalomyelitis induced by immunization with a myelin-derived peptide was examined in leptin-deficient, C57BL/6J-ob/ob mice, with or without leptin replacement, and in wild-type controls. Leptin replacement converted disease resistance to susceptibility in the C57BL/6J-ob/ob mice; this was accompanied by a switch from a Th2 to Th1 pattern of cytokine release and consequent reversal of Ig subclass production. Our findings suggest that leptin is required for the induction and maintenance of an effective proinflammatory immune response in the CNS.
Matarese
G
G
Cattedra di Immunologia, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita di Napoli "Federico II," Napoli, Italy.
Di Giacomo
A
A
Sanna
V
V
Lord
G M
GM
Howard
J K
JK
Di Tuoro
A
A
Bloom
S R
SR
Lechler
R I
RI
Zappacosta
S
S
Fontana
S
S
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D007271:Injections, Intradermal; D020738:Leptin / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D020738:Leptin; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011994:Recombinant Proteins