Universität zu Köln

Sanchez-Ruiz, Monica, Iorgu, Ana-Maria, Kuster, Florian, Hellmich, Martin ORCID: 0000-0001-5174-928X, Brunn, Anna and Deckert, Martina (2021). CD8 T cell-Derived Perforin and TNF-alpha Are Crucial Mediators of Neuronal Destruction in Experimental Autoimmune Enteric Ganglionitis. Am. J. Pathol., 191 (6). S. 1064 - 1077. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

In neuron-specific ovalbumin-transgenic CKTAC mice, antigen-specific OT-I CD8 T cells home to the enteric nervous system, where they attack and destroy neurons of the myenteric and submucosal plexus. Clinically, experimental autoimmune enteric ganglionitis (EAEG) manifests with gastrointestinal dysmotility and rapidly progresses to lethal ileus. Although interferon-g has been identified as capable of damaging neurons in EAEG, the role of perforin, Fas/FasL, and tumor necrosis factor-alpha (TNF-alpha) in this disease is still a matter of debate. Thus, CKTAC mice were adoptively transferred with either perforin(-/-) or wild-type OT-I CD8 T cells. In addition, CKTAC mice that had received wild-type OT-I CD8 T cells were treated by either anti-TNF-alpha or anti-FasL. Furthermore, wild-type OT-I CD8 T cells were adoptively transferred into CKTAC mice with neuron-specific deletion of Fas. Although neither inactivation of enteric neuronal Fas nor anti-FasL treatment improved the disease, the absence of perforin from OT-I CD8 T cells and anti-TNF-alpha treatment significantly ameliorated EAEG and prevented lethal ileus by rescue of enteric neurons. Thus, these experiments identify perforin and TNF-alpha as important in the pathogenesis of EAEG.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sanchez-Ruiz, Monica UNSPECIFIED UNSPECIFIED UNSPECIFIED Iorgu, Ana-Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuster, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellmich, Martin UNSPECIFIED orcid.org/0000-0001-5174-928X UNSPECIFIED Brunn, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-565131
DOI:	10.1016/j.ajpath.2021.02.021
Journal or Publication Title:	Am. J. Pathol.
Volume:	191
Number:	6
Page Range:	S. 1064 - 1077
Date:	2021
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 WEST-NILE-VIRUS; FAS; APOPTOSIS; INDUCTION; DEATH; NEUTRALIZATION; MECHANISMS; RECOVERY; ANTIGEN; BRAIN Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56513