Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo.
Besides being mandatory in the metabolic system, adipokines like leptin directly affect immunity. Leptin was found to be necessary in T helper 1 (Th1)-dependent inflammatory processes, whereas effects on Th2 cells are rarely understood. Here, we focused on leptin in T-helper cell polarization and in Th2-mediated intestinal inflammation in vivo. The induction of cytokine-producing Th1 or Th2 cells from naive CD4(+) T cells under polarizing conditions in vitro was generally decreased in cells from leptin-deficient ob/ob mice compared with wild-type mice. To explore the in vivo relevance of leptin in Th2-mediated inflammation, the model of oxazolone-induced colitis was employed in wild-type, ob/ob, and leptin-reconstituted ob/ob mice. Ob/ob mice were protected, whereas wild-type and leptin-reconstituted ob/ob mice developed colitis. The disease severity went in parallel with local production of the Th2 cytokine IL-13. A possible explanation for the protection of ob/ob mice in Th1- as well as in Th2-dependent inflammation is provided by a decreased expression of the key transcription factors for Th1 and Th2 polarization, T-bet and GATA-3, in naive ob/ob T cells. In conclusion, these results support the regulatory function of the adipokine leptin within T-cell polarization and thus in the acquired immune system and support the concept that there is a close interaction with the endocrine system.
Batra
Arvind
A
Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Gastroenterology, 12200 Berlin, Germany.
Okur
Besir
B
Glauben
Rainer
R
Erben
Ulrike
U
Ihbe
Jakob
J
Stroh
Thorsten
T
Fedke
Inka
I
Chang
Hyun-Dong
HD
Zeitz
Martin
M
Siegmund
Britta
B
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005759:Gastroenteritis / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D020738:Leptin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D000098815:T-bet Transcription Factor
D050990:GATA3 Transcription Factor; D020738:Leptin; D054411:Receptors, Leptin; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor