Defining the role of T cell-derived leptin in the modulation of hepatic or intestinal inflammation in mice

Abstract

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.

Leptin in immuno-rheumatological diseases

“…Among these factors, only leptin and adiponectin (and possibly resistin, adipsin and visfatin) are primarily produced by adipocytes, and they can therefore be properly classified as adipokines. 10 In particular, leptin is considered the prototypical adipokine.…”

Immunolocalisation of leptin in the digestive system of juvenile European sea bass (Dicentrarchus labrax)

“…Despite the name 'eosinophilic', EGCs may have different staining affinities, basophilic or eosinophilic, depending on the species considered and the conditions of fixation (Rocha & Chiarini-Garcia 2007). The involvement of leptin in inflammation is well-established in birds and mammals (Lõhmus et al 2004;Matarese et al 2005); in particular, it has been demonstrated that, in the mammalian intestine, lymphocytes release leptin at the inflammation site (Siegmund et al 2004;Fantuzzi et al 2005). Our data therefore suggest that leptin can be involved in immune and inflammatory responses in teleosts, in addition to its better-known role as a regulator of energy homeostasis.…”

Perinatal Immune Activation and Risk of Autism

“…Mast cells also express leptin and leptin receptors, a finding implicating paracrine or autocrine immunomodulatory effects of leptin on mast cells (Taildeman et al, 2009). Locally released leptin from T lymphocytes doesn't seem to play a major role in immunoregulation in mouse models of intestinal inflammation, suggesting other sources of leptin as critical in modulation of the inflammatory response (Fantuzzi et al, 2005). Despite evidence supporting the role of leptin in immune processes (Lago et al, 2008;Matarese et al, 2005), its precise role in inflammation remains incompletely understood.…”