Title: Ciliary neutrotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure.
Authors: Jovic, T
White, KE
Walkley, CR
Askmyr, M
Smeets, MF
Baker, EK
Maluenda, AC
Quach, JM
King, HA
Purton, LE
Issue Year: 2015
Publisher
Series Sci Rep:
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.
URI: https://publications.svi.edu.au/publications/2432
ISSN
Other Identifiers 21;5:15529
Publication type Article
Grant ID GNT1003339; GNT1006485
Find it online https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26487326/