Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells

Journal of Leukocyte Biology

Lewis T. Williams¹  Violeta Chitu²  Yee-Guide Yeung²  Minmei Huang¹  Haishan Lin¹  E. Richard Stanley²  Sayan Nandi²  Wenfeng Yu²  Suwen Wei² 

[1] Five Prime Therapeutics, Inc., San Francisco, California, USA Five Prime Therapeutics, Inc., San Francisco, California, USA Five Prime Therapeutics, Inc., San Francisco, California, USA;Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA; and

关键词: macrophages;    osteoclasts;    cytokines;    hematopoiesis;    inflammation;    tumor-associated macrophages;   

DOI  :  10.1189/jlb.1209822

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CSF-1 is broadly expressed and regulates macrophage and osteoclast development. The action and expression of IL-34, a novel CSF-1R ligand, were investigated in the mouse. As expected, huIL-34 stimulated macrophage proliferation via the huCSF-1R, equivalently to huCSF-1, but was much less active at stimulating mouse macrophage proliferation than huCSF-1. Like muCSF-1, muIL-34 and a muIL-34 isoform lacking Q81 stimulated mouse macrophage proliferation, CSF-1R tyrosine phosphorylation, and signaling and synergized with other cytokines to generate macrophages and osteoclasts from cultured progenitors. However, they respectively possessed twofold and fivefold lower affinities for the CSF-1R and correspondingly, lower activities than muCSF-1. Furthermore, muIL-34, when transgenically expressed in a CSF-1-dependent manner in vivo, rescued the bone, osteoclast, tissue macrophage, and fertility defects of Csf1op/op mice, suggesting similar regulation of CSF-1R-expressing cells by IL-34 and CSF-1. Whole-mount IL34 in situ hybridization and CSF-1 reporter expression revealed that IL34 mRNA was strongly expressed in the embryonic brain at E11.5, prior to the expression of Csf1 mRNA. QRT-PCR revealed that compared with Csf1 mRNA, IL34 mRNA levels were lower in pregnant uterus and in cultured osteoblasts, higher in most regions of the brain and heart, and not compensatorily increased in Csf1op/op mouse tissues. Thus, the different spatiotemporal expression of IL-34 and CSF-1 allows for complementary activation of the CSF-1R in developing and adult tissues.

【 授权许可】

Unknown