The granulocyte-colony stimulating factor receptor (G-CSFR) interacts with retinoic acid receptors (RARs) in the regulation of myeloid differentiation

• Published in: Journal of leukocyte biology Vol. 93; no. 2; pp. 235 - 243
• Main Authors: Chee, Lynette C. Y., Hendy, Jean, Purton, Louise E., McArthur, Grant A.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.02.2013
• Subjects: Animals; cytokines; Flow Cytometry; Granulocytes - cytology; Granulocytes - metabolism; granulopoiesis; Mice; Mice, Inbred C57BL; Mice, Knockout; Myelopoiesis - physiology; Receptors, Granulocyte Colony-Stimulating Factor - metabolism; Receptors, Retinoic Acid - metabolism; retinoids; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.1211609

Residual granulopoiesis persists in mice lacking both G‐CSFR and RARα, or RARγ; G‐CSFR is required for granulopoietic expansion seen with loss of RARγ. 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 RARγΔ/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.