Authors:	Girard-Madoux, Mathilde J. H. Ober-Blöbaum, Juliane L. Costes, Léa M. M. Kel, Junda M. Lindenbergh-Kortleve, Dicky J. Brouwers-Haspels, Inge Heikema, Astrid P. Samsom, Janneke N. Clausen, Björn
Title:	IL-10 control of CD11c+ myeloid cells is essential to maintain immune homeostasis in the small and large intestine
Online publication date:	10-Oct-2022
Year of first publication:	2016
Language:	english
Abstract:	Although IL-10 promotes a regulatory phenotype of CD11c(+) dendritic cells and macrophages in vitro, the role of IL-10 signaling in CD11c(+) cells to maintain intestinal tolerance in vivo remains elusive. To this aim, we generated mice with a CD11c-specific deletion of the IL-10 receptor alpha (Cd11c(cre)Il10ra(fl/fl)). In contrast to the colon, the small intestine of Cd11c(cre)Il10ra(fl/fl) mice exhibited spontaneous crypt hyperplasia, increased numbers of intraepithelial lymphocytes and lamina propria T cells, associated with elevated levels of T cell-derived IFN gamma and IL-17A. Whereas naive mucosal T-cell priming was not affected and oral tolerance to ovalbumin was intact, augmented T-cell function in the lamina propria was associated with elevated numbers of locally dividing T cells, expression of T-cell attracting chemokines and reduced T-cell apoptosis. Upon stimulation, intestinal IL-10Ra deficient CD11c(+) cells exhibited increased activation associated with enhanced IL-6 and TNFa production. Following colonization with Helicobacter hepaticus Cd11c(cre)Il10ra(fl/fl) mice developed severe large intestinal inflammation characterized by infiltrating T cells and increased levels of Il17a, Ifng, and Il12p40. Altogether these findings demonstrate a critical role of IL-10 signaling in CD11c(+) cells to control small intestinal immune homeostasis by limiting reactivation of local memory T cells and to protect against Helicobacter hepaticus-induced colitis.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7921
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/3.0/
Journal:	OncoTarget 7 22
Pages or article number:	32015 32030
Publisher:	Impact Journals LLC
Publisher place:	S.l.
Issue date:	2016
ISSN:	1949-2553
Publisher URL:	http://dx.doi.org/10.18632/oncotarget.8337
Publisher DOI:	10.18632/oncotarget.8337
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)