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Published online before print July 5, 2006

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(Journal of Leukocyte Biology. 2006;80:546-554.)
© 2006 by Society for Leukocyte Biology

Adipose tissue of human omentum is a major source of dendritic cells, which lose MHC Class II and stimulatory function in Crohn’s disease

Penelope A. Bedford^*, Vesna Todorovic^*, Edward D. A. Westcott, Alistair C. J. Windsor, Nicholas R. English^*, Hafid Omar Al-Hassi^*, Kankipati S. Raju, Sarah Mills and Stella C. Knight^*,1

^* Antigen Presentation Research Group and
St. Mark’s Institute for Intestinal and Colorectal Disorders, Imperial College London, Northwick Park and St. Mark’s Campus, Harrow, United Kingdom; and
Obstetrics & Gynaecology, St. Thomas’ Hospital, London, United Kingdom

¹ Correspondence: Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, 7W, Watford Road, Harrow HA1 3UJ, UK. E-mail: s.knight{at}imperial.ac.uk

Adipose tissue is reported to contain monocyte-like pre-adipocytes, which may mature into macrophages, contributing to local inflammation. Dendritic cells (DC) can be derived from monocytes and initiate and regulate primary immune responses. We hypothesized, therefore, that adipose tissue may provide DC involved in local immune activity. To test this, we studied cells from human omental adipose tissue samples from 17 patients with benign gynecological disease. The hypothesis that adipose tissue DC are involved in inflammatory disease was tested by comparing these cells with those from 18 patients with Crohn’s disease, where hypertrophy of adipose tissue suggests involvement in disease. A high proportion of the 1.33 ± 0.12 x 10⁵ CD45-positive cells/mg, obtained from control omenta, expressed CD11c, CD1a, and CD83; costimulatory molecules CD40, CD80, and CD86; and major histocompatibility complex (MHC) Class II but little CD14, CD16, or CD33. Omental cells showing morphological characteristics of DC were also observed. Metrizamide gradient-enriched DC from these populations were potent stimulators of primary proliferation of allogeneic T cells in mixed leukocyte reactions. Increased numbers of CD45+ cells from omentum of Crohn’s patients (4.50±1.08x10⁵ CD45+ cells/mg) contained higher percentages of CD11c+ and CD40+ cells (80.8±3.8% vs. 63.4±6, P=0.032; 77.9±4% vs. 58.8±6.5, P=0.029, respectively), but MHC Class II and stimulatory capacity were almost completely lost (P=<0.001), suggesting innate activation but lost capacity to stimulate adaptive immune responses. Granulocytes were also present amongst the omental cells from Crohn’s patients. Results indicated that omentum may provide DC, which could "police" local infections and contribute to and/or reflect local inflammatory activity.

Key Words: mucosa • inflammatory bowel disease • fatty acids