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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Animals, Autoimmunity, Cell Differentiation, Cells, Cultured, Citrobacter rodentium, Colitis, Enterobacteriaceae Infections, Leptin, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Obesity, Receptors, Leptin, STAT3 Transcription Factor, Signal Transduction, Th17 Cells