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The intricate interface between immune and metabolic regulation: a role for leptin in the pathogenesis of multiple sclerosis?
Author(s) -
Matarese Giuseppe,
Procaccini Claudio,
De Rosa Veronica
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0108022
Subject(s) - leptin , immune system , biology , experimental autoimmune encephalomyelitis , autoimmunity , proinflammatory cytokine , immunology , endocrinology , medicine , context (archaeology) , inflammation , paleontology , obesity
Over the last few years, a series of molecules known to play a function in metabolism has also been shown to play an important role in the regulation of the immune response. In this context, the adipocyte‐derived hormone leptin has been shown to regulate the immune response in normal as well as in pathological conditions. More specifically, it has been shown that conditions of reduced leptin production (i.e., genetic leptin deficiency, anorexia nervosa, malnutrition) are associated with increased susceptibility to infections. Conversely, immune‐mediated disorders such as autoimmune disorders are associated with increased secretion of leptin and production of proinflammatory, pathogenic cytokines. Leptin could represent the “missing link” among immune response, metabolic function, and nutritional status. Indeed, more recently, leptin‐deficient mice have been shown to be resistant to a series of experimentally induced autoimmune disorders including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Normal wild‐type mice show increased secretion of leptin in serum upon EAE induction, and brain inflammatory infiltrates stain positive for leptin. Finally, leptin neutralization with leptin antagonists improves the EAE course by profoundly altering intracellular signaling of myelin‐reactive T cells and increasing the number of regulatory forkhead/winged helix transcription factor 3 + CD4 + T cells. These data suggest that leptin can be considered as a link among immune tolerance, metabolic state, and autoimmunity and that strategies aimed at interfering with the leptin axis could represent innovative, therapeutic tools for autoimmune disorders.