Cutting edge: Leptin-induced RORγt expression in CD4+ T cells promotes Th17 responses in systemic lupus erythematosus.

Abstract

Th17 CD4(+) cells promote inflammation and autoimmunity. In this study, we report that Th17 cell frequency is reduced in ob/ob mice (that are genetically deficient in the adipokine leptin) and that the administration of leptin to ob/ob mice restored Th17 cell numbers to values comparable to those found in wild-type animals. Leptin promoted Th17 responses in normal human CD4(+) T cells and in mice, both in vitro and in vivo, by inducing RORγt transcription. Leptin also increased Th17 responses in (NZB × NZW)F1 lupus-prone mice, whereas its neutralization in those autoimmune-prone mice inhibited Th17 responses. Because Th17 cells play an important role in the development and maintenance of inflammation and autoimmunity, these findings envision the possibility to modulate abnormal Th17 responses via leptin manipulation, and they reiterate the link between metabolism/nutrition and susceptibility to autoimmunity.

• Authors: Yiyun Yu, Yaoyang Liu, Fu-Dong Shi, Hejian Zou, Giuseppe Matarese, Antonio La Cava
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 190 Issue 7 Pg. 3054-8 (Apr 01 2013) ISSN: 1550-6606 [Electronic] United States
• PMID: 23447682 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Leptin
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Receptors, Leptin

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Disease Models, Animal
• Gene Expression Regulation
• Humans
• Leptin (genetics, metabolism)
• Lupus Erythematosus, Systemic (genetics, immunology)
• Mice
• Mice, Knockout
• Nuclear Receptor Subfamily 1, Group F, Member 3 (genetics)
• Receptors, Leptin (genetics, metabolism)
• Th17 Cells (immunology, metabolism)
• Transcription, Genetic