Defining the role of T cell-derived leptin in the modulation of hepatic or intestinal inflammation in mice.
The role of leptin in the immune system has been well established. While adipocytes represent the major source, leptin production by lymphocytes, infiltrating at the site of inflammation, was recently demonstrated. However, the significance of this locally released leptin remains unresolved. In the present study, two models in which absence of leptin-signalling is associated with protection were employed: the model of ConA-induced hepatitis and the CD4(+)CD45Rb(high) transfer model of colitis. For the ConA model, scid mice were reconstituted with either WT or leptin-deficient (ob/ob) CD4(+) T cells. Eight weeks post transfer, ConA was injected and serum ALT, TNFalpha, leptin as well as liver mononuclear cell activation and histological signs of inflammation were evaluated. No difference between recipients of WT or ob/ob cells was observed for any of the parameters evaluated. In the second model, either WT or ob/ob CD4(+)CD45Rb(high) cells were transferred into scid mice. No histological differences were detected, although recipients of ob/ob cells showed higher weight loss compared to recipients of WT cells. Spontaneous production of IL-6 from colon cultures obtained from recipients of ob/ob cells was reduced compared to recipients of WT cells, whereas stimulation of lamina propria lymphocytes with leptin resulted in a higher IFNgamma release in recipients of ob/ob cells compared to recipients of WT cells. In conclusion, the present study provides evidence that T cell-derived leptin does not play a major role in the regulation of the inflammatory process, indicating that the adipose tissue is the critical player in the immune-modulating effects of leptin.
Fantuzzi
G
G
Department of Medicine I, Charité, Campus Benjamin Franklin, Berlin, Germany.
Sennello
J A
JA
Batra
A
A
Fedke
I
I
Lehr
H A
HA
Zeitz
M
M
Siegmund
B
B
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003092:Colitis / Q000276:immunology*; D003106:Colon / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology; D006505:Hepatitis / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D020738:Leptin / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D016513:Mice, SCID
D020738:Leptin; D003208:Concanavalin A; D017493:Leukocyte Common Antigens