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Non-Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice.

Publication ,  Journal Article
Lin, L; Hwang, B-J; Li, N; Googe, P; Diaz, LA; Miao, E; Vilen, B; Thomas, NE; Ting, J; Liu, Z
Published in: J Immunol
November 15, 2020

BP180 (also termed type XVII collagen) is a hemidesmosomal protein and plays a critical role in cell-cell matrix adhesion in the skin; however, its other biological functions are largely unclear. In this study, we generated a BP180 functional-deficient mouse strain by deleting its extracellular domain of humanized NC16A (termed ΔNC16A mice). We found that BP180 is expressed by bone marrow mesenchymal stem cells (BM-MSC), and its functional deficiency leads to myeloid hyperplasia. Altered granulopoiesis in ΔNC16A mice is through bone marrow stromal cells evidenced by bone marrow transplantation. Furthermore, the level of G-CSF in bone marrow and circulation were significantly increased in ΔNC16A mice as compared with wild-type mice. The increased G-CSF was accompanied by an increased activation of the NF-κB signaling pathway in bone marrow and BM-MSC of ΔNC16A mice. Blockade of G-CSF restored normal granulopoiesis in ΔNC16A mice. Inhibition of NF-κB signaling pathway significantly reduces the release of G-CSF from ΔNC16A BM-MSC in vitro and the level of serum G-CSF in ΔNC16A mice. To our knowledge, these findings provide the first direct evidence that BP180 plays an important role in granulopoiesis through regulating NF-κB signaling pathway in BM-MSC.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2020

Volume

205

Issue

10

Start / End Page

2786 / 2794

Location

United States

Related Subject Headings

  • Signal Transduction
  • Protein Domains
  • Non-Fibrillar Collagens
  • Neutrophils
  • NF-kappa B
  • Mice, Transgenic
  • Mice
  • Mesenchymal Stem Cells
  • Leukopoiesis
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lin, L., Hwang, B.-J., Li, N., Googe, P., Diaz, L. A., Miao, E., … Liu, Z. (2020). Non-Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice. J Immunol, 205(10), 2786–2794. https://doi.org/10.4049/jimmunol.2000784
Lin, Lin, Bin-Jin Hwang, Ning Li, Paul Googe, Luis A. Diaz, Ed Miao, Barbara Vilen, Nancy E. Thomas, Jenny Ting, and Zhi Liu. “Non-Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice.J Immunol 205, no. 10 (November 15, 2020): 2786–94. https://doi.org/10.4049/jimmunol.2000784.
Lin L, Hwang B-J, Li N, Googe P, Diaz LA, Miao E, et al. Non-Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice. J Immunol. 2020 Nov 15;205(10):2786–94.
Lin, Lin, et al. “Non-Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice.J Immunol, vol. 205, no. 10, Nov. 2020, pp. 2786–94. Pubmed, doi:10.4049/jimmunol.2000784.
Lin L, Hwang B-J, Li N, Googe P, Diaz LA, Miao E, Vilen B, Thomas NE, Ting J, Liu Z. Non-Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice. J Immunol. 2020 Nov 15;205(10):2786–2794.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2020

Volume

205

Issue

10

Start / End Page

2786 / 2794

Location

United States

Related Subject Headings

  • Signal Transduction
  • Protein Domains
  • Non-Fibrillar Collagens
  • Neutrophils
  • NF-kappa B
  • Mice, Transgenic
  • Mice
  • Mesenchymal Stem Cells
  • Leukopoiesis
  • Immunology