Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure.
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.
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.|Department of Clinical Genetics, Lund University, Lund, Sweden.
Maria
M
Askmyr
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.
Kirby E
KE
White
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.
Tanja
T
Jovic
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.
Hannah A
HA
King
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.
Julie M
JM
Quach
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.
Ana C
AC
Maluenda
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.|Department of Medicine at St. Vincent's Hospital, The University of Melbourne, Fitzroy, Vic. 3065, Australia.
Emma K
EK
Baker
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.
Monique F
MF
Smeets
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.|Department of Medicine at St. Vincent's Hospital, The University of Melbourne, Fitzroy, Vic. 3065, Australia.
Carl R
CR
Walkley
Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic. 3065, Australia.|Department of Medicine at St. Vincent's Hospital, The University of Melbourne, Fitzroy, Vic. 3065, Australia.
Louise E
LE
Purton
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D016723:Bone Remodeling / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D060833:Cellular Microenvironment / Q000235:genetics; D020934:Ciliary Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006410:Hematopoiesis / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics
D020934:Ciliary Neurotrophic Factor; D050822:Cytokine Receptor gp130