Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development.
Abstract
In a forward genetic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice for
aberrant immune function, we identified mice with a syndromic disorder marked by growth
retardation, diabetes, premature death, and severe lymphoid and myeloid hypoplasia
together with diminished T cell-independent (TI) antibody responses. The causative
mutation was in Pdia6, an essential gene encoding protein disulfide isomerase A6 (PDIA6),
an oxidoreductase that functions in nascent protein folding in the endoplasmic reticulum.
The immune deficiency caused by the Pdia6 mutation was, with the exception of a residual
T cell developmental defect, completely rescued in irradiated wild-type recipients
of PDIA6-deficient bone marrow cells, both in the absence or presence of competition.
The viable hypomorphic allele uncovered in these studies reveals an essential role
for PDIA6 in hematopoiesis, but one extrinsic to cells of the hematopoietic lineage.
We show evidence that this role is in the proper folding of Wnt3a, BAFF, IL-7, and
perhaps other factors produced by the extra-hematopoietic compartment that contribute
to the development and lineage commitment of hematopoietic cells.
Type
Journal articleSubject
LymphocytesT-Lymphocytes
Cell Line
Myeloid Cells
Animals
Mice, Inbred C57BL
Humans
Mice
Interleukin-7
Hematopoiesis
Female
Male
B-Cell Activating Factor
Protein Disulfide-Isomerases
HEK293 Cells
Wnt3A Protein
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https://hdl.handle.net/10161/23464Published Version (Please cite this version)
10.1084/jem.20190006Publication Info
Choi, Jin Huk; Zhong, Xue; Zhang, Zhao; Su, Lijing; McAlpine, William; Misawa, Takuma;
... Beutler, Bruce (2020). Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development.
The Journal of experimental medicine, 217(4). 10.1084/jem.20190006. Retrieved from https://hdl.handle.net/10161/23464.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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