title: The granulocyte-colony stimulating factor receptor (G-CSFR) interacts with retinoic acid receptors (RARs) in the regulation of myeloid differentiation.
abstract: The key roles of RARs and G-CSFR in the regulation of granulopoiesis have been well-documented. In this study, we sought to investigate the interaction between G-CSFR and RARs in myeloid differentiation of adult mice through conditional deletion of RARα or RARγ on a G-CSFR(-/-) background and by pharmacological intervention of WT and G-CSFR(-/-) mice with a pan-RAR inverse agonist, NRX194310. Our findings show that residual granulopoiesis still persists in mice doubly null for G-CSFR and RARα or RARγ, confirming that RARs and G-CSFR are dispensable in maintaining residual granulopoiesis. Moreover, an increase in mature myeloid cells was seen in the conditional RARγ(Δ/Δ) mice and WT mice treated with NRX194310, likely mediated through increased G-CSF production. However, with the loss of G-CSFR, this expansion in granulopoiesis was attenuated, supporting the hypothesis that G-CSFR signaling interacts with RARs in the regulation of myeloid differentiation.
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Lynette C Y
authors.initials: LC
authors.lastname: Chee
authors.forename: Jean
authors.initials: J
authors.lastname: Hendy
authors.forename: Louise E
authors.initials: LE
authors.lastname: Purton
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038042:Myelopoiesis / Q000502:physiology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor; D018168:Receptors, Retinoic Acid