2nd Annual BMRP Investigator Meeting - Abstract

Role of Leptin Receptors Expression on T Lymphocytes in Intestinal Inflammation

Giamila Fantuzzi

Department of Medicine, University of Colorado Health Sciences Center (Denver, U.S.A.)

Leptin regulates appetite through binding to the long isoform of its receptor in the hypothalamus.  Although leptin also regulates intestinal inflammation, it is still unknown whether a direct effect of leptin on lymphocytes is required.

To clarify whether expression of leptin receptors on T lymphocytes modulates intestinal inflammation in mice, we used the model of colitis induced by transfer of CD4⁺CD45RB^high (RB^high) cells into scid mice.  To this aim, wild type or leptin receptor-deficient (db/db) RB^high cells were transferred into scid mice and development of colitis evaluated.

Leptin receptors were expressed on both wild type RB^high and RB^low cells.  Intestinal lymphocytes of mice with colitis expressed high levels of leptin compared with healthy controls, whereas the opposite was true for serum leptin levels.  Transfer of RB^high cells from leptin receptor-deficient db/db mice induced a delayed disease compared to transfer of wild type cells.  A high rate of apoptosis in lamina propria lymphocytes and reduced cytokine production were observed early on in scid mice receiving db/db RB^high cells.  These effects were not due to the high levels of glucocorticoids present in db/db mice, since administration of corticosterone to wild type mice failed to reproduce this phenomenon.  High expression of PPARg was observed in the colon of recipients of db/db compared with wild type cells.  Furthermore, freshly isolated db/db RB^high cells produced low levels of IFNg.  Despite delayed onset of colitis, as disease progressed, differences between mice receiving wild type or db/db cells were no longer apparent.

These results suggest that leptin affects the immune response partly by acting on the long isoform of its receptor expressed on T lymphocytes.