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  • Review Article
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Immune modulation by butyrophilins

Key Points

  • Butyrophilins have recently materialized as a new family of immunoregulators that are similar to the co-stimulatory and co-inhibitory family of B7 molecules.

  • For a subset of butyrophilins, recombinant proteins and antibodies have been shown to modulate a variety of T cell functions, including the enhancement or attenuation of T cell activation, regulatory T cell differentiation from naive T cells, thymic cell selection and T cell localization.

  • There is much still to be learned about the function of butyrophilins. The mode of interaction between butyrophilins and other cell-surface molecules is generally poorly understood, and several butyrophilin family members have yet to be ascribed any biological function.

  • Human genetic data indicates that butyrophilins can be modifiers of disease susceptibility.

  • Although evolving data highlight the potential role of butyrophilins in the modulation of human disease, much more needs to be understood before contemplating their use as targets for therapeutic intervention.

Abstract

The B7 family of co-stimulatory molecules has an important role in driving the activation and inhibition of immune cells. Evolving data have shown that a related family of molecules — the butyrophilins — have similar immunomodulatory functions to B7 family members and may represent a novel subset of co-stimulatory molecules. These studies have taken the field by surprise, as the butyrophilins were previously thought to only be important in lactation and milk production. In this Review, we describe the expression patterns of the various members of the butyrophilin family and explore their immunomodulatory functions. In particular, we emphasize the contribution of butyrophilins to immune homeostasis and discuss the potential of targeting these molecules for therapeutic purposes.

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Figure 1: Structural comparison of the B7 and butyrophilin superfamilies.
Figure 2: Modulation of T cell activity by butyrophilins.
Figure 3: The many functions of the butyrophilin 3A subfamily.

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Acknowledgements

The authors would like to thank A. Gardet for critical reading of the manuscript.

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Correspondence to Joanne L. Viney.

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H.A.A. is currently employed by Amgen. J.L.V. is currently employed by Biogen Idec.

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Arnett, H., Viney, J. Immune modulation by butyrophilins. Nat Rev Immunol 14, 559–569 (2014). https://doi.org/10.1038/nri3715

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