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Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development.

Publication ,  Journal Article
Choi, JH; Zhong, X; Zhang, Z; Su, L; McAlpine, W; Misawa, T; Liao, T-C; Zhan, X; Russell, J; Ludwig, S; Li, X; Tang, M; Anderton, P ...
Published in: The Journal of experimental medicine
April 2020

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.

Duke Scholars

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Published In

The Journal of experimental medicine

DOI

EISSN

1540-9538

ISSN

0022-1007

Publication Date

April 2020

Volume

217

Issue

4

Start / End Page

e20190006

Related Subject Headings

  • Wnt3A Protein
  • T-Lymphocytes
  • Protein Disulfide-Isomerases
  • Myeloid Cells
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lymphocytes
  • Interleukin-7
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
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Choi, J. H., Zhong, X., Zhang, Z., Su, L., McAlpine, W., Misawa, T., … Beutler, B. (2020). Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development. The Journal of Experimental Medicine, 217(4), e20190006. https://doi.org/10.1084/jem.20190006
Choi, Jin Huk, Xue Zhong, Zhao Zhang, Lijing Su, William McAlpine, Takuma Misawa, Tzu-Chieh Liao, et al. “Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development.The Journal of Experimental Medicine 217, no. 4 (April 2020): e20190006. https://doi.org/10.1084/jem.20190006.
Choi JH, Zhong X, Zhang Z, Su L, McAlpine W, Misawa T, et al. Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development. The Journal of experimental medicine. 2020 Apr;217(4):e20190006.
Choi, Jin Huk, et al. “Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development.The Journal of Experimental Medicine, vol. 217, no. 4, Apr. 2020, p. e20190006. Epmc, doi:10.1084/jem.20190006.
Choi JH, Zhong X, Zhang Z, Su L, McAlpine W, Misawa T, Liao T-C, Zhan X, Russell J, Ludwig S, Li X, Tang M, Anderton P, Moresco EMY, Beutler B. Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development. The Journal of experimental medicine. 2020 Apr;217(4):e20190006.

Published In

The Journal of experimental medicine

DOI

EISSN

1540-9538

ISSN

0022-1007

Publication Date

April 2020

Volume

217

Issue

4

Start / End Page

e20190006

Related Subject Headings

  • Wnt3A Protein
  • T-Lymphocytes
  • Protein Disulfide-Isomerases
  • Myeloid Cells
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lymphocytes
  • Interleukin-7
  • Immunology