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Perforin and Human Diseases

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MACPF/CDC Proteins - Agents of Defence, Attack and Invasion

Part of the book series: Subcellular Biochemistry ((SCBI,volume 80))

Abstract

Natural killer (NK) cells and cytotoxic T lymphocytes (CTL) use a highly toxic pore-forming protein perforin (PFN) to destroy cells infected with intracellular pathogens and cells with pre-cancerous transformations. However, mutations of PFN and defects in its expression can cause an abnormal function of the immune system and difficulties in elimination of altered cells. As discussed in this chapter, deficiency of PFN due to the mutations of its gene, PFN1, can be associated with malignancies and severe immune disorders such as familial hemophagocytic lymphohistiocytosis (FHL) and macrophage activation syndrome. On the other hand, overactivity of PFN can turn the immune system against autologous cells resulting in other diseases such as systemic lupus erythematosus, polymyositis, rheumatoid arthritis and cutaneous inflammation. PFN also has a crucial role in the cellular rejection of solid organ allografts and destruction of pancreatic β-cells resulting in type 1 diabetes. These facts highlight the importance of understanding the biochemical characteristics of PFN.

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Abbreviations

AD:

Atopic dermatitis

CD4:

Cluster of differentiation 4

CD8:

Cluster of differentiation 8

CDC:

Cholesterol dependent cytolysin

CIA:

Collagen-induced arthritis

CL:

Cytotoxic lymphocytes

CTL:

Cytotoxic T lymphocytes

DM:

Dermatomyositis

DMD:

Duchenne muscular dystrophy

EGF:

Epidermal growth factor regulatory domain

FasL:

Fas ligand, a type-II transmembrane protein that belongs to the TNF family

FHL:

Familial hemophagocytic lymphohistiocytosis

FHL-2:

Familial hemophagocytic lymphohistiocytosis type 2

HGMD:

Human gene mutation database

LCMV:

Lymphocytic choriomeningitis virus

LCMV-GP:

Glycoprotein of lymphocytic choriomeningitis virus

MACPF:

Membrane attack complex-PFN

MHC:

Major histocompatibility complex

NK:

Natural killer

PFN:

Perforin

PM:

Polymyositis

SLE:

Systemic lupus erythematosus

SLEDAI:

SLE disease activity index

Tc1:

Type 1 CD8 T cells

Tc2:

Type 2 CD8 T cells

TNF:

Tumor necrosis factor

WT:

Wild type

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Authors and Affiliations

  1. Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000, Ljubljana, Slovenia

    Omar Naneh & Apolonija Bedina Zavec

  2. Department of Allergology Rheumatology and Clinical Immunology Children’s Hospital, University Medical Center Ljubljana, Bohoričeva 20, 1525, Ljubljana, Slovenia

    Tadej Avčin

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  1. Omar Naneh
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  1. National Institute of Chemistry, Ljubljana, Slovenia, Laboratory for Molecular Biology and Nanobiotechnology, Ljubljana, Slovenia

    Gregor Anderluh

  2. Division of Structural Biology, University of Oxford Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom

    Robert Gilbert

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Naneh, O., Avčin, T., Bedina Zavec, A. (2014). Perforin and Human Diseases. In: Anderluh, G., Gilbert, R. (eds) MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Subcellular Biochemistry, vol 80. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8881-6_11

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