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Murine Models of Familial Cytokine Storm Syndromes

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Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disease caused by mutations in effectors and regulators of cytotoxicity in cytotoxic T cells (CTL) and natural killer (NK) cells. The complexity of the immune system means that in vivo models are needed to efficiently study diseases like HLH. Mice with defects in the genes known to cause primary HLH (pHLH) are available. However, these mice only develop the characteristic features of HLH after the induction of an immune response (typically through infection with lymphocytic choriomeningitis virus). Nevertheless, murine models have been invaluable for understanding the mechanisms that lead to HLH. For example, the cytotoxic machinery (i.e., the transport of cytotoxic vesicles and the release of granzymes and perforin after membrane fusion) was first characterized in the mouse. Experiments in murine models of pHLH have emphasized the importance of cytotoxic cells, antigen-presenting cells (APC), and cytokines in hyperinflammatory positive feedback loops (e.g., cytokine storms). This knowledge has facilitated the development of treatments for human HLH, some of which are now being tested in the clinic.

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Authors and Affiliations

  1. Division of Immunology, University Children’s Hospital Zurich, Zurich, Switzerland

    Benjamin Volkmer & Jana Pachlopnik Schmid

  2. Department of Immunology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany

    Peter Aichele

  3. University of Zurich, Zurich, Switzerland

    Jana Pachlopnik Schmid

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  1. Benjamin Volkmer
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  2. Peter Aichele
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Correspondence to Jana Pachlopnik Schmid .

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  1. UAB School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Randy Q. Cron

  2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Edward M. Behrens

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Volkmer, B., Aichele, P., Pachlopnik Schmid, J. (2019). Murine Models of Familial Cytokine Storm Syndromes. In: Cron, R., Behrens, E. (eds) Cytokine Storm Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-030-22094-5_28

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