Leptin receptor signaling in T cells is required for Th17 differentiation

The hormone leptin plays a key role in energy homeostasis, and the absence of either leptin or its receptor (LepR) leads to severe obesity and metabolic disorders. To avoid indirect effects and to address the cell-intrinsic role of leptin signaling in the immune system, we conditionally targeted Lep...

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Published inThe Journal of immunology (1950) Vol. 194; no. 11; pp. 5253 - 5260
Main Authors Reis, Bernardo S, Lee, Kihyun, Fanok, Melania H, Mascaraque, Cristina, Amoury, Manal, Cohn, Lillian B, Rogoz, Aneta, Dallner, Olof S, Moraes-Vieira, Pedro M, Domingos, Ana I, Mucida, Daniel
Format Journal Article
LanguageEnglish
Published United States 01.06.2015
Subjects
Animals
Autoimmunity - genetics
Autoimmunity - immunology
Cell Differentiation - genetics
Cell Differentiation - immunology
Cells, Cultured
Citrobacter rodentium - immunology
Colitis - immunology
Enterobacteriaceae Infections - immunology
Leptin - immunology
Lymphocyte Activation - genetics
Lymphocyte Activation - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity - genetics
Obesity - immunology
Receptors, Leptin - genetics
Receptors, Leptin - immunology
Signal Transduction - genetics
Signal Transduction - immunology
STAT3 Transcription Factor - genetics
Th17 Cells - cytology
Th17 Cells - immunology
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Summary:The hormone leptin plays a key role in energy homeostasis, and the absence of either leptin or its receptor (LepR) leads to severe obesity and metabolic disorders. To avoid indirect effects and to address the cell-intrinsic role of leptin signaling in the immune system, we conditionally targeted LepR in T cells. In contrast with pleiotropic immune disorders reported in obese mice with leptin or LepR deficiency, we found that LepR deficiency in CD4(+) T cells resulted in a selective defect in both autoimmune and protective Th17 responses. Reduced capacity for differentiation toward a Th17 phenotype by lepr-deficient T cells was attributed to reduced activation of the STAT3 and its downstream targets. This study establishes cell-intrinsic roles for LepR signaling in the immune system and suggests that leptin signaling during T cell differentiation plays a crucial role in T cell peripheral effector function.
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Current address: IBD Center, Laboratory of Immunology in Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy.
Current address: Sackler Institute of Graduate Biomedical Studies, New York University School of Medicine, New York, NY, USA.
These authors contributed equally for this work
Current address: Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1402996