Perinodal adipose tissue and fatty acid composition of lymphoid tissues in patients with and without Crohn's disease and their implications for the etiology and treatment of CD.

The physiological bases for roles of adipose tissue and fatty acids in the symptoms and dietary treatments of Crohn's disease are poorly understood. The hypothesis developed from experiments on rodents that perinodal adipocytes are specialized to provision adjacent lymphoid tissues was tested by comparing the composition of triacylglycerol fatty acids in homologous samples of mesenteric adipose tissue and lymph nodes from patients with or without Crohn's disease. Mesenteric perinodal and other adipose tissue, and lymph nodes, were collected during elective surgery for Crohn's disease and other conditions. Fatty acids were extracted, identified, and quantified by thin-layer and gas-liquid chromatography. Perinodal adipose tissue contained more unsaturated fatty acids than other adipose tissue in controls, as reported for other mammals, but site-specific differences were absent in Crohn's disease. Lipids from adipose and lymphoid tissues had more saturated fatty acids, but fewer polyunsaturates in Crohn's disease patients than controls. In adipose tissue samples, depletion of n-3 polyunsaturates was greatest, but n-6 polyunsaturates, particularly arachidonic acid, were preferentially reduced in lymphoid cells. Ratios of n-6/n-3 polyunsaturates were higher in adipose tissue but lower in lymphoid cells in Crohn's disease patients than in controls. Site-specific differences in fatty acid composition in normal human mesentery are consistent with local interactions between lymph node lymphoid cells and adjacent adipose tissue. But these site-specific properties are absent in Crohn's disease, causing anomalies in composition of lymphoid cell fatty acids, which may explain the efficacy of elemental diets containing oils rich in n-6 polyunsaturates.

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

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 10(5) 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+/-1.08 x 10(5) 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.