Leptin Metabolically Licenses T Cells for Activation To Link Nutrition and Immunity

Donte C. Saucillo, Valerie A. Gerriets, John Sheng, Jeffrey C. Rathmell and Nancie J. MacIver. J Immunol. (2014) 192:136-144.

Speaker: Chi-En Hsieh (謝季恩)                          Time: 14:10~15:00, Mar. 4, 2015

Commentator: Dr. Pin Ling (凌 斌 老師)            Place: Room 601

Abstract

Activated T cells must consume nutrients by glucose uptake and metabolism to obtain energy to increase cytokine production and proliferation (1). According to the previous studies, leptin can regulate adaptive immune responses toward Th1 phenotype and be a proinflammatory cytokine (2). However, the mechanisms of leptin regulation in adaptive immunity and T cell function are not clear. In this study, the authors wanted to know whether leptin gave some signals to link metabolism and adaptive immunity. First of all, the authors confirmed that decreased leptin levels induced by fasting were associated with inflammatory cytokines production and glucose metabolism defects of activated T cells. Then they found additional exogenous leptin increased inflammatory cytokines production from activated T cells. Moreover, whether inflammatory cytokines production, activated T cells proliferation or glucose metabolism needed signals through leptin receptors. In addition, the authors demonstrated that the effects of leptin between activated T cell function and glucose metabolism were cell intrinsic and the expression of glucose transporter Glut1 for glucose metabolism was regulated by leptin. Importantly, Glut1 overexpression also could rescue T cell function and metabolism when there was no leptin. Furthermore, T cell metabolic and functional defects were rescued by leptin administration both in vitro and in vivo experiments. In conclusion, the results indicated that leptin regulated Glut1 to metabolize glucose and .provide energy to maintain T cell functions in the sufficient nutritional status.

References

1.     Jacobs SR et al. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol. (2008) 180: 4476–4486.

2.     Procaccini C et al. Leptin as an immunomodulator. Mol Aspects Med. (2012) 33: 35-45.