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.
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.
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Ilgiz A
authors.initials: IA
authors.lastname: Mufazalov
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Tommy
authors.initials: T
authors.lastname: Regen
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schelmbauer
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Kuschmann
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.|Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Muratova
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Alexei
authors.initials: A
authors.lastname: Nikolaev
authors.affiliation: Faculty of Biology, Medicine and Health University of Manchester, Manchester, United Kingdom.
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.affiliation: Faculty of Biology, Medicine and Health University of Manchester, Manchester, United Kingdom.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinteaux
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000378:metabolism; D015415:Biomarkers; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis*; D018390:Gene Targeting; D016130:Immunophenotyping; D007375:Interleukin-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D017252:CD3 Complex; D016207:Cytokines; D007375:Interleukin-1; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I