Leptin receptor expression and signaling in lymphocytes: kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice.
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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.
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The role of leptin in regulating immune function appears to be permissive.
“The role of leptin in regulating immune function appears to be a permissive one (33), because there might exist a critical leptin threshold above which leptin has no major additional physiologic effect on neuroendocrine or immune function (7).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [33]
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Self-citation
- Authors
- Papathanassoglou, E., El-Haschimi, K., Li, X. C., Matarese, G., Strom, T., & Mantzoros, C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Institute for Experimental Endocrinology and Oncology (IT)
- Corresponding author
- Papathanassoglou, Elizabeth
- Mantzoros, Christos
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-06
- Volume
- 176
- Issue
- 12
- Pages
- 7745-7752
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1939446637
- Cited by
- 258
- References
- 39
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 12 · 2022: 11 · 2021: 14 · 2020: 8 · 2019: 15 · 2018: 9 · 2017: 9 · 2016: 13 · 2015: 19 · 2014: 21 · 2013: 17 · 2012: 20
- FWCI
- 8.49
- Type
- journal article
- Language
- en
- Open access
- green
- ktisis.cut.ac.cy
- Licence
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Ktisis at Cyprus University of Technology (Cyprus University of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Public Health Service (R0-158785)
- National Institute of Allergy and Infectious Diseases (P01AI041521)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- leptin, leptin receptor, lymphocyte activation, lymphocyte survival, STAT3 signaling, T cell proliferation, B cells, Fas-mediated apoptosis, anti-apoptotic effects, high-fat diet, diet-induced obesity, leptin resistance
- MeSH terms
- Animals, Antibodies, Monoclonal, Cell Survival, Cells, Cultured, Dietary Fats, Kinetics, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Mutant Strains, Receptors, Cell Surface, Signal Transduction, Lymphocyte Subsets, B-Lymphocyte Subsets, T-Lymphocyte Subsets, Apoptosis, CD3 Complex, Diet, Fat-Restricted, fas Receptor, Leptin, STAT3 Transcription Factor, Mice, Receptors, Leptin
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