GM-CSF- and IRF4-Dependent Signaling Can Regulate Myeloid Cell Numbers and the Macrophage Phenotype during Inflammation
Ming-Chin Lee, Derek C Lacey, Andrew J Fleetwood, Adrian Achuthan, John A Hamilton, Andrew D Cook
JOURNAL OF IMMUNOLOGY | AMER ASSOC IMMUNOLOGISTS | Published : 2019
Studies have demonstrated the importance of a GM-CSF→IFN regulatory factor 4 (IRF4)→CCL17 pathway, first identified in monocytes/macrophages, for arthritic pain and disease development. In this study, we further investigated the involvement of this new pathway in shaping the inflammatory response using the zymosan-induced peritonitis (ZIP) model. ZIP (8 mg of zymosan, i.p., day 0) was induced in C57BL/6 wild-type (WT), GM-CSF-/- , Irf4-/- , and Ccl17E/E mice. In comparison with WT mice, GM-CSF-/- and Irf4-/- mice had a reduced ZIP response, as judged by a reduced number of neutrophils and macrophages in the peritoneal cavity. Moreover, the phenotype of the ZIP macrophages was altered by a la..View full abstract
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Awarded by National Health and Medical Research Council of Australia
This work was supported by Grant 1043147 (to A.D.C. and J.A.H.) and a Senior Principal Research Fellowship from the National Health and Medical Research Council of Australia (to J.A.H.).