Thursday, July 16, 2015: 12:00 AM
Salon Dublin, Second Floor (Maritim Hotel)
Paolo Biancheri, MD
,
Barts and The London School of Medicine and Dentistry, London, United Kingdom
Antonio Di Sabatino, MD
,
First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
Giulia Fornasa, PhD
,
European institute of oncology, Milan, Italy
Cinzia Papadia, MD
,
Department of Gastroenterology, Norwich Medical School, Norwich, United Kingdom
Eleanor Wood, MD
,
Academic Department of Medical and Surgical Gastroenterology, Homerton University Hospital, London, United Kingdom
Ray Shidrawi, MD
,
Academic Department of Medical and Surgical Gastroenterology, Homerton University Hospital, London, United Kingdom
Alastair Forbes, MD
,
Department of Gastroenterology, Norwich Medical School, Norwich, United Kingdom
Gino Roberto Corazza, MD
,
First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
Maria Rescigno, PhD
,
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
Thomas MacDonald, PhD
,
CIID, Barts and The London School of Medicine and Dentistry, London, United Kingdom
Background & Aims. TSLP is down-regulated in untreated CD mucosa, whereas its levels are unknown in refractory CD (RCD). We evaluated duodenal TSLP and TSLP receptor (TSLP-R) expression in RCD, and we studied TSLP effects on pro-inflammatory cytokine production by RCD biopsies.
Methods. TSLP and TSLP-R expression was studied on duodenal biopsies from 12 RCD, 14 uncomplicated CD patients and 14 control subjects by qRT-PCR, confocal microscopy and immunoblotting. IL-17A, IL-6 and TNF-α were measured by ELISA in the supernatants of duodenal biopsies from 6 RCD patients cultured ex vivo with or without rhTSLP.
Results. TSLP gene and protein expression was significantly reduced in the duodenum of RCD and untreated CD patients compared to treated CD patients and control subjects, without differences between RCD and untreated CD patients. TSLP-R was expressed in the duodenal mucosa, without significant differences between RCD, untreated and treated CD patients and control subjects. rhTSLP significantly inhibited IL-17A, IL-6 and TNF-α release by RCD biopsies (from 62±6 to 20±3 pg/ml; from 1892±341 to 632±172 pg/ml; from 181±42 to 67±15 pg/ml, respectively).
Conclusions. Reduced TSLP expression may sustain the pro-inflammatory cytokine increase observed in RCD. Further studies are needed to clarify the influence of TSLP reduction on mucosal immunosurveillance in RCD.
