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J Biol Chem. 2016 Oct 14;291(42):22086-22092. Epub 2016 Aug 26.

Proof of Principle for a T Lymphocyte Intrinsic Function of Coronin 1A.

Author information

1
From the Department for Pharmacology and Genetics, Medical University Innsbruck, Peter Mayr Strasse 1a, AT-6020 Innsbruck, Austria kerstin.siegmund@i-med.ac.at.
2
From the Department for Pharmacology and Genetics, Medical University Innsbruck, Peter Mayr Strasse 1a, AT-6020 Innsbruck, Austria.
3
From the Department for Pharmacology and Genetics, Medical University Innsbruck, Peter Mayr Strasse 1a, AT-6020 Innsbruck, Austria Gottfried.Baier@i-med.ac.at.

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.

KEYWORDS:

animal model; autoimmunity; cell signaling; immunodeficiency; lymphocyte

PMID:
27566541
PMCID:
PMC5063991
DOI:
10.1074/jbc.M116.748012
[Indexed for MEDLINE]
Free PMC Article

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