Universität zu Köln

Sanchez-Ruiz, Monica, Brunn, Anna, Montesinos-Rongen, Manuel, Rudroff, Claudia, Hartmann, Melanie, Schlueter, Dirk, Pfitzer, Gabriele and Deckert, Martina (2019). Enteric Murine Ganglionitis Induced by Autoimmune CD8 T Cells Mimics Human Gastrointestinal Dysmotility. Am. J. Pathol., 189 (3). S. 540 - 552. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

Inflammatory bowel diseases frequently cause gastrointestinal dysmotility, suggesting that they may also affect the enteric nervous system. So far, the precise mechanisms that lead to gastrointestinal dysmotility in inflammatory bowel diseases have not been elucidated. To determine the effect of CD8 T cells on gastrointestinal motility, transgenic mice expressing ovalbumin on enteric neurons were generated. In these mice, adoptive transfer of ovalbumin-specific OT-I CD8 T cells induced severe enteric ganglionitis. CD8 T cells homed to submucosal and myenteric plexus neurons, 60% of which were lost, clinically resulting in severely impaired gastrointestinal transition. Anti interferon-gamma treatment rescued neurons by preventing their up-regulation of major histocompatibility complex class I antigen, thus preserving gut motility. These preclinical murine data translated well into human gastrointestinal dysmotility. In a series of 30 colonic biopsy specimens from patients with gastrointestinal dysmotility, CD8 T cell mediated ganglionitis was detected that was followed by severe loss of enteric neurons (74.8%). Together, the preclinical and clinical data support the concept that autoimmune CD8 T cells play an important pathogenetic role in gastrointestinal dysmotility and may destroy enteric neurons.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sanchez-Ruiz, Monica UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunn, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Montesinos-Rongen, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudroff, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlueter, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfitzer, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-155395
DOI:	10.1016/j.ajpath.2018.11.016
Journal or Publication Title:	Am. J. Pathol.
Volume:	189
Number:	3
Page Range:	S. 540 - 552
Date:	2019
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1525-2191
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOLECULAR MIMICRY; BOWEL; ACTIVATION; NEURONS; DISEASE; FEATURES Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15539