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On guard: coronin proteins in innate and adaptive immunity

Nature Reviews Immunology volume 13, pages 510–518 (2013)Cite this article

Subjects

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.

Abstract

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.

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Figure 1: The roles of coronin 1 and coronin 4 in macrophages.
Figure 2: The role of coronin 1 in the survival of naive T cells.

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Acknowledgements

The authors thank D. Moshous, K. Siegmund, M. Stiess and A. Vinet for critical reading and comments, A. Roulier for illustrations and members of the laboratory for discussions. R.J. is a Max Cloëtta medical research fellow. Work in the laboratory of J.P. is financed by the Canton of Basel and the Swiss National Science Foundation.

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  1. Biozentrum, University of Basel, Klingelbergstrasse 50, Basel, 4056, Switzerland

    Jean Pieters & Rajesh Jayachandran

  2. Department of Biomedicine, University of Basel and University Hospital Basel, Hebelstrasse 20, Basel, CH-4031, Switzerland

    Philipp Müller

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Correspondence to Jean Pieters.

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Patents related to this work have been filed (WO2007110385A2 and WO2009112542A1) by the University of Basel, Switzerland.

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Glossary

Actin-related protein 2/3 complex

(ARP2/3 complex). A complex composed of seven proteins, including ARP2, ARP3, and the ARP complex subunit 1 (ARPC1)–ARPC5. The complex has little activity on its own but, when bound to an ARP2/3 nucleation-promoting factor, it is activated to generate new actin filaments from pre-existing filaments.

Calcium signalling

Triggered by phospholipase Cγ1-mediated hydrolysis of phosphatidylinositol-4,5-bisphosphate into inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol. Binding of Ins(1,4,5)P3 to its receptor on the endoplasmic reticulum (ER) membrane causes the release of calcium ions from ER stores. This opens calcium-release-activated calcium channels in the plasma membrane, leading to the influx of calcium ions. The increased intracellular calcium ion concentration activates calcineurin, protein kinase C and several other enzymes that are required for gene expression.

Nuclear receptor co-repressor 1 complex

(NCOR1 complex). A large multimeric complex that mediates active transcriptional repression of various inflammatory genes in the basal resting state. Repression mediated by NCOR1 complexes occurs via modification of the chromatin structure of NCOR1by associated histone deacetylases. Some of the best characterized nuclear receptors that are transcriptionally repressed by NCOR1 complexes include the thyroid receptor, the retinoic acid receptor and the glucocorticoid receptor.

Liver X receptors

(LXRs). Oxysterol-activated nuclear receptors that regulate cholesterol homeostasis and that contribute to the repression of pro-inflammatory genes.

Immunological synapse

A large junctional structure that is formed between a T cell and an antigen-presenting cell (APC); it consists of molecules that are required for adhesion and signalling. This structure is important in establishing T cell adhesion and polarity, it is influenced by the cytoskeleton and it transduces highly controlled secretory signals, thereby facilitating the directed release of cytokines or lytic granules towards the APC or the target cell.

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Pieters, J., Müller, P. & Jayachandran, R. On guard: coronin proteins in innate and adaptive immunity. Nat Rev Immunol 13, 510–518 (2013). https://doi.org/10.1038/nri3465

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