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Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure.

Askmyr, Maria LU ; White, Kirby E; Jovic, Tanja; King, Hannah A; Quach, Julie M; Maluenda, Ana C; Baker, Emma K; Smeets, Monique F; Walkley, Carl R and Purton, Louise E (2015) In Scientific Reports 5.
Abstract
The gp130 receptor and its binding partners play a central role in cytokine signalling. Ciliary neurotrophic factor (CNTF) is one of the cytokines that signals through the gp130 receptor complex. CNTF has previously been shown to be a negative regulator of trabecular bone remodelling and important for motor neuron development. Since haematopoietic cell maintenance and differentiation is dependent on the bone marrow (BM) microenvironment, where cells of the osteoblastic lineage are important regulators, we hypothesised that CNTF may also have important roles in regulating haematopoiesis. Analysis of haematopoietic parameters in male and female Cntf(-/-) mice at 12 and 24 weeks of age revealed altered B lymphopoiesis. Strikingly, the B... (More)
The gp130 receptor and its binding partners play a central role in cytokine signalling. Ciliary neurotrophic factor (CNTF) is one of the cytokines that signals through the gp130 receptor complex. CNTF has previously been shown to be a negative regulator of trabecular bone remodelling and important for motor neuron development. Since haematopoietic cell maintenance and differentiation is dependent on the bone marrow (BM) microenvironment, where cells of the osteoblastic lineage are important regulators, we hypothesised that CNTF may also have important roles in regulating haematopoiesis. Analysis of haematopoietic parameters in male and female Cntf(-/-) mice at 12 and 24 weeks of age revealed altered B lymphopoiesis. Strikingly, the B lymphocyte phenotype differed based on sex, age and also the BM microenvironment in which the B cells develop. When BM cells from wildtype mice were transplanted into Cntf(-/-) mice, there were minimal effects on B lymphopoiesis or bone parameters. However, when Cntf(-/-) BM cells were transplanted into a wildtype BM microenvironment, there were changes in both haematopoiesis and bone parameters. Our data reveal that haematopoietic cell-derived CNTF has roles in regulating BM B cell lymphopoiesis and both trabecular and cortical bone, the latter in a sex-dependent manner. (Less)
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organization
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Contribution to journal
publication status
published
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in
Scientific Reports
volume
5
publisher
Nature Publishing Group
external identifiers
  • pmid:26487326
  • wos:000363121000001
  • scopus:84944937335
ISSN
2045-2322
DOI
10.1038/srep15529
language
English
LU publication?
yes
id
17f5f8c8-f7d4-4ba2-87fb-54979e867749 (old id 8148756)
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http://www.ncbi.nlm.nih.gov/pubmed/26487326?dopt=Abstract
date added to LUP
2015-11-03 18:54:06
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2017-01-01 06:33:57
@article{17f5f8c8-f7d4-4ba2-87fb-54979e867749,
  abstract     = {The gp130 receptor and its binding partners play a central role in cytokine signalling. Ciliary neurotrophic factor (CNTF) is one of the cytokines that signals through the gp130 receptor complex. CNTF has previously been shown to be a negative regulator of trabecular bone remodelling and important for motor neuron development. Since haematopoietic cell maintenance and differentiation is dependent on the bone marrow (BM) microenvironment, where cells of the osteoblastic lineage are important regulators, we hypothesised that CNTF may also have important roles in regulating haematopoiesis. Analysis of haematopoietic parameters in male and female Cntf(-/-) mice at 12 and 24 weeks of age revealed altered B lymphopoiesis. Strikingly, the B lymphocyte phenotype differed based on sex, age and also the BM microenvironment in which the B cells develop. When BM cells from wildtype mice were transplanted into Cntf(-/-) mice, there were minimal effects on B lymphopoiesis or bone parameters. However, when Cntf(-/-) BM cells were transplanted into a wildtype BM microenvironment, there were changes in both haematopoiesis and bone parameters. Our data reveal that haematopoietic cell-derived CNTF has roles in regulating BM B cell lymphopoiesis and both trabecular and cortical bone, the latter in a sex-dependent manner.},
  articleno    = {15529},
  author       = {Askmyr, Maria and White, Kirby E and Jovic, Tanja and King, Hannah A and Quach, Julie M and Maluenda, Ana C and Baker, Emma K and Smeets, Monique F and Walkley, Carl R and Purton, Louise E},
  issn         = {2045-2322},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure.},
  url          = {http://dx.doi.org/10.1038/srep15529},
  volume       = {5},
  year         = {2015},
}