Leptin receptor expression and signaling in lymphocytes: Kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice

Elizabeth Papathanassoglou, Karim El-Haschimi, Xian Chang Li, Giuseppe Matarese, Terry Strom, Christos Mantzoros

Research output: Contribution to journalArticle

Abstract

Leptin has direct effects not only on neuroendocrine function and metabolism, but also on T cell-mediated immunity. We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4+, CD8+, B cells, and monocyte/macrophages. ObR expression is up-regulated following cell activation, but with different kinetics, in different lymphocyte subsets. Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. Leptin also promotes lymphocyte survival in vitro by suppressing Fas-mediated apoptosis. B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. Moreover, CD4+ T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. Taken together, our data further support the notion that nutritional status acting via leptin-dependent mechanisms may alter the nature and vigor of the immune response.

Original languageEnglish
Pages (from-to)7745-7752
Number of pages8
JournalJournal of Immunology
Volume176
Issue number12
Publication statusPublished - Jun 15 2006

ASJC Scopus subject areas

  • Immunology

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    Papathanassoglou, E., El-Haschimi, K., Li, X. C., Matarese, G., Strom, T., & Mantzoros, C. (2006). Leptin receptor expression and signaling in lymphocytes: Kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice. Journal of Immunology, 176(12), 7745-7752.