Poster (15W226)

Evidence of On-going Activation of the Mucosal Immune System in Irritable Bowel Syndrome


Moloney G, Fanning A, MacSharry J, Darby T, Edelstein E, O'Malley D, Hall LJ Heuston S, Collins F, Scanlan N, Beltran C, Craig O, Dinan T, Cryan J, Hyland N, Shanahan F , Quigley EM, Melgar S, Nally K


APC Microbiome Institute, University College Cork


Irritable Bowel Syndrome (IBS) is a gastrointestinal disorder of unknown etiology affecting as many as 10-20% of adults. Abdominal pain and disordered defecation are core symptoms and in most sufferers are episodic. Alterations in the gut microbiota and aberrant immune responses have also been described by some investigators in IBS.


In this study we focused on the innate and adaptive immune response in mucosal tissue and plasma from IBS patients.


We analyzed, in mucosal biopsy tissue of controls and IBS patients, the expression of 35 genes which code for both type I and II interferon (IFN) pathways and IFN stimulated genes (ISGs). We also analyzed the expression of the IFN-regulated and T-cell selective CXCL10/CXCR3 chemokine system in both mucosal biopsy tissue and plasma. In addition, we investigated both the distribution and functional status of T cells in control and IBS mucosal tissue using a combination of qRT-PCR, immunofluorescence staining, cellular activation experiments with anti-CD3/CD28 and quantitation of cytokine production.


We found significantly altered expression of components of the type I interferon pathway and the IFN-regulated CXCL10/CXCR3 chemokine system in IBS tissue. While we did not find any evidence of increased numbers of T cells in IBS mucosal tissue, IBS biopsy tissue displayed hyper-responsiveness to anti-CD3/CD28 T cell stimulation as manifested by production of IL-17, CXCL9, CXCL10, MCP-1 and MIP-1β.


Collectively, these studies provide compelling evidence of on-going activation of the mucosal immune system in IBS and are consistent with an immune response to an unidentified, organic trigger in IBS.

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