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The Unusual Immune System of the Naked Mole-Rat

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The Extraordinary Biology of the Naked Mole-Rat

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1319))

Abstract

The immune system plays a critical role in host defense to pathogens, tissue homeostasis, cancer development, and several aging-associated chronic inflammatory diseases. The naked mole-rat (Heterocephalus glaber) is a subterranean rodent with both extraordinary longevity and cancer-resistant phenotypes. Unlike the immune system of standard laboratory rodents, that of the naked mole-rat features a higher myeloid-to-lymphoid ratio, lacks natural killer cells, has higher pro-inflammatory cytokine production in macrophages, and exhibits a novel LPS-responsive neutrophil subset that highly expresses several antimicrobials. Given these unusual features, the potential involvement of the naked mole-rat’s immune system in their longevity and cancer-resistance remains enigmatic. In this chapter, we summarize the current knowledge of the immune system in the naked mole-rat, including the immune cell repertoire, the primary and secondary lymphoid organs, and the inflammatory responses to the pathogenic stimulation such as bacterial toxins. We compare these findings to published studies of the other subterranean rodents and discuss how the environmental factors in which they have evolved may have influenced their immune function.

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Photo Credit: Ben Passarelli

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Acknowledgements

We gratefully acknowledge support from Calico. We thank Nimrod Rubinstein for reviewing an earlier draft of this manuscript and for many helpful discussions. Figures are drawn using Biorender, Stanford.

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Authors and Affiliations

  1. Calico Life Sciences LLC, South San Francisco, CA, USA

    Tzuhua Lin & Rochelle Buffenstein

  2. Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX, USA

    Rochelle Buffenstein

Authors
  1. Tzuhua Lin
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  2. Rochelle Buffenstein
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Editors and Affiliations

  1. Calico Life Sciences LLC, South San Francisco, CA, USA

    Rochelle Buffenstein

  2. Laboratory of Integrative NeuroscienceDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA

    Thomas J. Park

  3. Department of Psychology, University of Toronto Mississauga, Mississauga, ON, Canada

    Melissa M. Holmes

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Lin, T., Buffenstein, R. (2021). The Unusual Immune System of the Naked Mole-Rat. In: Buffenstein, R., Park, T.J., Holmes, M.M. (eds) The Extraordinary Biology of the Naked Mole-Rat. Advances in Experimental Medicine and Biology, vol 1319. Springer, Cham. https://doi.org/10.1007/978-3-030-65943-1_12

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