Authors:	Mufazalov, Ilgiz A. Regen, Tommy Schelmbauer, Carsten Kuschmann, Janina Muratova, Alisa M. Nikolaev, Alexei Müller, Werner Pinteaux, Emmanuel Waisman, Ari
Title:	Generation of a novel T cell specific interleukin-1 receptor type 1 conditional knock out mouse reveals intrinsic defects in survival, expansion and cytokine production of CD4 T cells
Online publication date:	15-Sep-2022
Year of first publication:	2016
Language:	english
Abstract:	Interleukin-1 (IL-1) plays a crucial role in numerous inflammatory diseases via action on its only known signaling IL-1 receptor type 1 (IL-1R1). To investigate the role of IL-1 signaling in selected cell types, we generated a new mouse strain in which exon 5 of the Il1r1 gene is flanked by loxP sites. Crossing of these mice with CD4-Cre transgenic mice resulted in IL-1R1 loss of function specifically in T cells. These mice, termed IL-1R1ΔT, displayed normal development under steady state conditions. Importantly, isolated CD4 positive T cells retained their capacity to differentiate toward Th1 or Th17 cell lineages in vitro, and strongly proliferated in cultures supplemented with either anti-CD3/CD28 or Concanavalin A, but, as predicted, were completely unresponsive to IL-1β administration. Furthermore, IL-1R1ΔT mice were protected from gut inflammation in the anti-CD3 treatment model, due to dramatically reduced frequencies and absolute numbers of IL-17A and interferon (IFN)-γ producing cells. Taken together, our data shows the necessity of intact IL-1 signaling for survival and expansion of CD4 T cells that were developed in an otherwise IL-1 sufficient environment.
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-7766
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	PLoS one 11 8
Pages or article number:	e0161505
Publisher:	PLoS
Publisher place:	Lawrence, Kan.
Issue date:	2016
ISSN:	1932-6203
Publisher URL:	http://dx.doi.org/10.1371/journal.pone.0161505
Publisher DOI:	10.1371/journal.pone.0161505
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)