title: Proof of Principle for a T Lymphocyte Intrinsic Function of Coronin 1A.
abstract: Coronins are evolutionarily conserved proteins that were originally identified as modulators of actin-dependent processes. Studies analyzing complete Coronin 1a knock-out mice have shown that this molecule is an important regulator of naive T cell homeostasis and it has been linked to immune deficiencies as well as autoimmune disorders. Nevertheless, because Coronin 1A is strongly expressed in all leukocyte subsets, it is not conclusive whether or not this phenotype is attributed to a T cell-intrinsic function of Coronin 1A. To address this research question, we have generated a T cell-specific Coronin 1a knock-out mouse (Coro1afl/fl× Cd4[Cre]). Deletion of Coronin 1A specifically in T cells led to a strong reduction in T cell number and a shift toward the effector/memory phenotype in peripheral lymphoid organs when compared with Cd4[Cre] mice expressing wild-type Coronin 1A. In contrast to peripheral lymphoid tissue, thymocyte number and subsets were not affected by the deletion of Coronin 1a Furthermore, T cell-specific Coronin 1a knock-out mice were largely resistant to the induction of autoimmunity when tested in the myelin oligoglycoprotein-induced EAE mouse model of multiple sclerosis. Thus, the phenotype of T cell-specific Coronin 1a deletion resembles the phenotype observed with conventional (whole body) Coronin 1a knock-out mice. In summary, our findings provide formal proof of the predominant T cell-intrinsic role of Coronin 1A.
authors: From the Department for Pharmacology and Genetics, Medical University Innsbruck, Peter Mayr Strasse 1a, AT-6020 Innsbruck, Austria kerstin.siegmund@i-med.ac.at.
authors: Kerstin
authors: K
authors: Siegmund
authors: From the Department for Pharmacology and Genetics, Medical University Innsbruck, Peter Mayr Strasse 1a, AT-6020 Innsbruck, Austria.
authors: Victoria
authors: V
authors: Klepsch
authors: From the Department for Pharmacology and Genetics, Medical University Innsbruck, Peter Mayr Strasse 1a, AT-6020 Innsbruck, Austria.
authors: Natascha
authors: N
authors: Hermann-Kleiter
authors: From the Department for Pharmacology and Genetics, Medical University Innsbruck, Peter Mayr Strasse 1a, AT-6020 Innsbruck, Austria Gottfried.Baier@i-med.ac.at.
authors: Gottfried
authors: G
authors: Baier
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007156:Immunologic Memory; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000276:immunology*; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D008840:Microfilament Proteins; C072061:coronin proteins
keywords: animal model; autoimmunity; cell signaling; immunodeficiency; lymphocyte