Proof of Principle: Coronin 1A – An Intrinsic Modulator of T Lymphocyte Function [Signal Transduction]

August 26th, 2016 by Siegmund, K., Klepsch, V., Hermann-Kleiter, N., Baier, G.

Coronins are evolutionarily conserved proteins that were originally identified as modulators of actin-dependent processes. Studies analyzing complete Coronin 1a knockout mice have shown that this molecule is an important regulator of T cell homeostasis and it has been linked to immune deficiencies as well as autoimmune disorders. Nevertheless, since 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 knockout mouse (Coro1afl/fl x Cd4[Cre]). Deletion of Coro1a specifically in T cells led to a strong reduction in T cell number and a shift towards the effector/memory phenotype in peripheral lymphoid organs when compared to Cd4[Cre] mice expressing wild-type Coro1a. In contrast to peripheral lymphoid tissue, thymocyte number and subsets were not affected by the deletion of Coro1a. Furthermore, T cell-specific Coro1a knockout mice were largely resistant to the induction of autoimmunity when tested in the MOG-induced EAE mouse model of multiple sclerosis. Thus, the phenotype of T cell-specific Coro1a deletion resembles the phenotype observed with conventional (whole body) Coro1a knockout mice. In summary, our findings provide formal proof of the predominant T cell-intrinsic role of Coronin 1A.