title: Intestinal APCs of the endogenous nanomineral pathway fail to express PD-L1 in Crohn's disease.
abstract: Crohn's disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn's disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn's disease show selective failure in PD-L1 expression. Therefore, in Crohn's disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease.
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Robertson
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, UK.
authors.forename: Carolin T
authors.initials: CT
authors.lastname: Haas
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, UK.
authors.forename: Laetitia C
authors.initials: LC
authors.lastname: Pele
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, UK.
authors.forename: Tom P
authors.initials: TP
authors.lastname: Monie
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Charalambos
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Miles
authors.initials: M
authors.lastname: Parkes
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Hewitt
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, UK.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Powell
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000473:pathology; D060890:B7-H1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D008297:Male
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human