On guard: coronin proteins in innate and adaptive immunity

Key Points Coronin molecules are highly conserved proteins that are expressed throughout the eukaryotic kingdom. There are seven mammalian genes that encode coronins, several of which are expressed in immune cells. Both in mice and in humans, coronin mutations have been associated with immunodeficiencies and resistance to autoimmunity. Several coronin molecules associate with F-actin but whether or not mammalian coronins are directly involved in F-actin modulation remains to be elucidated. Coronin 4 has an important role in the derepression of various inflammatory genes by being a core component of nuclear receptor co-repressor 1 complexes. Coronin 1 is one of the most conserved and best-characterized coronin family members. It is abundantly expressed in leukocytes and protects mycobacteria in macrophages from lysosomal delivery through the activation of the calcium–calcineurin signalling pathway. In lymphocytes, coronin 1 also regulates the calcium–calcineurin signalling pathway and is essential for the survival of naive T cells. In mice and humans, coronin 1 deletion and/or mutation is associated with profound naive T cell deficiency. Moreover, mice that are deficient in coronin 1 are resistant to autoimmune stimuli. Coronins were first characterized on the basis of their interactions with the actin cytoskeleton and were later linked to immune dysfunction. In this short, focused Review, the authors discuss the emerging roles of coronins in immune cell signalling. Recent work has implicated members of the evolutionarily conserved family of coronin proteins — in particular coronin 1 — in immune homeostasis. Coronins are involved in processes as diverse as pathogen survival in phagocytes and homeostatic T cell signalling. Notably, in both mice and humans, coronin mutations are associated with immune deficiencies and resistance to autoimmunity. In this article, we review what is currently known about these conserved molecules and discuss a potential common mechanism that underlies their diverse activities, which seem to involve cytoskeletal interactions as well as calcium–calcineurin signalling.