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* = Presenting author

P006 Transcriptomic profiling of intestinal macrophages isolated from patients reveals a profound gene expression reprogramming underlying IBD pathogenesis

Dharmasiri S.*1,2, Garrido Martin E.M.2, Sanchez-Elsner T.2, Cummings J.R.F.1

1Southampton General Hospital, Department of Gastroenterology, Southampton, United Kingdom 2University of Southampton, Department of Clinical and Experimental Sciences, Southampton, United Kingdom

Background

Macrophages play a major role as effector cells of the innate immune system and are vital for intestinal tissue homeostasis. An altered function of intestinal macrophages may contribute to the development and propagation of intestinal inflammation in IBD. However, all data available come from mouse models, human whole tissue or in vitro derived macrophages from blood monocytes. We have isolated intestinal macrophages from patients and healthy subjects and analysed their transcriptome in order to study the intrinsic role that macrophages play in the pathogenesis of IBD.

Methods

Fresh colonic mucosal tissue biopsies from 10 CD patients, 10 UC patients and 10 healthy controls were disaggregated to cell suspensions and sorted using fluorescence-activated cell sorting. RNA from intestinal macrophages, identified as CD163+CD14+CD3- population, was extracted and subjected to RNA sequencing. Differential Gene Expression analysis and pathway analysis were performed between the groups.

Results

The transcriptomic analysis revealed that the gene expression profile of the intestinal macrophages from IBD is dramatically reprogrammed. Differential Gene Expression analysis revealed 1287 DEGs between macrophages from UC patients and healthy controls; 840 DEGs between macrophages from CD patients and healthy controls and 20 DEGs between macrophages from UC and CD patients (1.5 fold change and FDR <0.1).

Figure 1. Differential gene expression analysis and principle component analysis.

Conclusion

This is the first study to describe the transcriptome of intestinal macrophages from active lesions of patients with IBD by high throughput RNAseq. We show that the transcriptome of these macrophages is profoundly different from those taken from healthy subjects. These results suggest that macrophages play an important role in the propagation of inflammation and we have identified a number of molecules that should be investigated as potential therapeutic targets.