C-type lectins in immunity and homeostasis

Abstract

The C-type lectins are a superfamily of proteins that recognize a broad repertoire of ligands and that regulate a diverse range of physiological functions. Most research attention has focused on the ability of C-type lectins to function in innate and adaptive antimicrobial immune responses, but these proteins are increasingly being recognized to have a major role in autoimmune diseases and to contribute to many other aspects of multicellular existence. Defects in these molecules lead to developmental and physiological abnormalities, as well as altered susceptibility to infectious and non-infectious diseases. In this Review, we present an overview of the roles of C-type lectins in immunity and homeostasis, with an emphasis on the most exciting recent discoveries.

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Fig. 1: Representative C-type lectin structures.
Fig. 2: Role of C-type lectins in cancer.
Fig. 3: Cellular functions of transmembrane C-type lectins in antimicrobial immunity.
Fig. 4: C-type lectins in autoimmunity.

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Acknowledgements

The authors thank the Wellcome Trust, the UK Medical Research Council (MRC), the MRC Centre for Medical Mycology at the University of Aberdeen and Arthritis Research UK for financial support. The authors apologize to colleagues whose many valuable contributions could not be cited owing to space constraints.

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Nature Reviews Immunology thanks S. Gringhuis, J. Ruland and D. Sancho for their contribution to the peer review of this work.

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Correspondence to Gordon D. Brown.

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Imperial College London C-type Lectins website: http://www.imperial.ac.uk/research/animallectins/ctld/classes/C-type1.html

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Supplementary information

Glossary

Proteoglycans

Proteins that are heavily glycosylated, normally with one or more covalently attached glycosaminoglycans. They are found in the extracellular matrix, in connective tissue and on the surface of cells.

Autosomal dominant polycystic kidney disease

One of the most common monogenic diseases found in humans; it is characterized by structurally abnormal renal tubules that form fluid-filled cysts.

Fibroblastic reticular cells

(FRCs). Myofibroblast stromal cells of mesenchymal origin found in lymphoid tissues. They express the CLEC2 ligand podoplanin, and they create a three-dimensional network facilitating antigen transport and leukocyte migration.

Myeloid-derived suppressor cells

(MDSCs). A heterogeneous population of cells of myeloid origin that have the ability to suppress T cell responses in multiple diseases. MDSCs can be further divided into monocytic MDSCs and neutrophilic MDSCs.

Pattern recognition receptors

(PRRs). Receptors that bind to conserved molecular patterns normally found in pathogens (pathogen-associated molecular patterns (PAMPs)) but also to structures associated with cellular damage (damage-associated molecular patterns (DAMPs)). Examples of PAMPs include β-glucans and lipopolysaccharide. Examples of DAMPs include F-actin and spliceosome-associated protein 130 (SAP130).

Neutrophil extracellular traps

(NETs). Extracellular structures consisting of DNA, hydrolytic enzymes and other antimicrobial components that are produced following the induction of a defined cell death programme in neutrophils. NETs, and similar structures produced by other cell types, trap and kill microorganisms extracellularly.

Adjuvants

In the immunological context, adjuvants are compounds that potentiate or boost the immunogenicity of an antigen. Adjuvants are required to improve the effectiveness of vaccines, as they stimulate innate immune responses that promote the development of adaptive immunity to the vaccine antigens.

Autophagy

An intracellular uptake mechanism that induces the membrane enclosure of intracellular components and their targeting to the lysosomal pathway for degradation.

Cytotoxic T lymphocyte

(CTL). CTLs are CD8+ T cells that can kill infected, transformed or damaged cells. CTLs recognize cellular antigens that are presented in the context of MHC class I molecules, which can trigger their cytotoxic activities either directly, through the release of perforin, granzymes and granulysin that enter and kill the target cells, or indirectly, through expression of FAS ligand, which binds to FAS on the surface of target cells, inducing a death-associated intracellular signalling pathway.

Genome-wide association studies

(GWAS). Genetic sequencing studies used to determine whether a genetic variant (normally a single-nucleotide polymorphism) found within a population is associated with a trait of interest, such as a specific disease.

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Brown, G.D., Willment, J.A. & Whitehead, L. C-type lectins in immunity and homeostasis. Nat Rev Immunol 18, 374–389 (2018). https://doi.org/10.1038/s41577-018-0004-8

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