P398 Leptin controls immune cell composition and activity in acquired generalised lipodystrophy with combined Crohn’s disease
J. F. Ziegler*1, C. Böttcher2, H. Wu1, R. Glauben1, B. Siegmund1, C. Weidinger1,3
1Charité - Universitätsmedizin Berlin, Department of Gastroenterology, Rheumatology and Infectious Disease, Campus Benjamin Franklin, Berlin, Germany, 2Charité – Universitätsmedizin Berlin, Laboratory of Molecular Psychiatry and Department of Neuropsychiatry, DZNE Berlin, Berlin, Germany, 3Berlin Institute of Health, Berlin, Germany
Leptin, a fat-derived adipokine, has been suggested to modulate intestinal inflammation in mice. However, clinical evidence regarding its immune-stimulatory potential in Crohn’s disease remains sparse. We here describe a 21-year-old patient with the solitaire combination of acquired generalised lipodystrophy and combined Crohn’s disease (AGLCD) featuring a complete lack of visceral and subcutaneous adipose tissue, absent leptin production and severe intestinal inflammation, who received daily injections with 2.5 mg recombinant
Using mass and flow cytometry, immunohistochemistry (IHC), ELISA and Seahorse analyses, we characterised the effects of rLeptin substitution on the patient’s immune cell composition and function
In the absence of mesenteric fat, we observed a unique immune cell composition in the peripheral blood of the AGLCD patient, characterised by reduced frequencies of NK cells and CD14+ monocytes, an accumulation of lipid droplets in monocytes, NK and CD8+ T cells, decreased expression of CCR7 on T cells and an increased expression of CD38 on T and NK cells compared with healthy donors and Crohn’s disease patients. Treatment of the AGLCD patient with rLeptin reduced the lipid droplet contents of immune cells and
Our results suggest that leptin might play a crucial role in human immune cell homeostasis and that in the setting of a pre-existing inflammatory condition leptin therapy might fuel inflammation and increase disease activity via the induction of TNFα-producing cells, which can be reversed by TNFα-blockade.