Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II.

Abstract:

:Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects, that harbor independent missense mutations in Caspase 10. These encode amino acid substitutions that decrease caspase activity and interfere with death receptor-induced apoptosis, particularly that stimulated by Fas ligand and TRAIL. These results provide evidence that inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II.

journal_name

Cell

journal_title

Cell

authors

Wang J,Zheng L,Lobito A,Chan FK,Dale J,Sneller M,Yao X,Puck JM,Straus SE,Lenardo MJ

doi

10.1016/S0092-8674(00)80605-4

subject

Has Abstract

pub_date

1999-07-09 00:00:00

pages

47-58

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(00)80605-4

journal_volume

98

pub_type

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