title: Regulation of myeloid progenitor cell proliferation/survival by IL-31 receptor and IL-31.
abstract: OBJECTIVE
  Interleukin (IL)-31 is a recently discovered helical cytokine. Its receptor consists of a ligand-specific IL-31 receptor (IL-31R) subunit and a receptor chain that is shared with Oncostatin M (OSM), called OSM-Rbeta. Because OSM-Rbeta-deficient animals have reduced hematopoietic progenitor cells (HPC) and OSM has effects on and is involved in homeostasis of HPC, we studied whether IL-31 and IL-31R play a role in hematopoiesis.
  
  
  METHODS
  IL-31R(-/-) mice and their littermate wild-type (WT) controls were assessed for absolute numbers and cycling status of bone marrow and spleen HPC (colony-forming unit granulocyte macrophage [CFU-GM], burst-forming unit erythroid [BFU-E], colony-forming unit granulocyte, erythrocyte, macrophage, megakaryocyte). Recombinant IL-31 was evaluated for stimulation, enhancement, or inhibition of colony formation by HPC, and for survival-enhancing effects on HPC subjected to growth-factor withdrawal and delayed addition of grown factors. Hematopoietic stem cells (HSC) from WT and IL-31R(-/-) mice were compared for competitive repopulating capacity in lethally irradiated congenic mice.
  
  
  RESULTS
  IL-31R(-/-) mice demonstrated significantly decreased absolute numbers and cycling status of immature subsets of HPC in bone marrow bone and spleen compared to WT mice. There were no significant differences in absolute numbers of more mature subsets of WT and IL-31R(-/-) bone marrow CFU-GM. WT but not IL-31R(-/-) bone marrow CFU-GM responded to synergistic stimulation by combinations of cytokines. While IL-31 had neither colony-stimulating, -enhancing, or -inhibiting activity for bone marrow HPC, it did enhance survival of these HPC in the context of delayed addition of growth factors. No significant differences were detected in competitive repopulating HSC activity between WT and IL-31R(-/-) bone marrow cells.
  
  
  CONCLUSIONS
  IL-31R is involved in positive regulation of absolute numbers and cycling status of immature subsets of HPC in vivo. While IL-31 in vitro does not modulate proliferation of HPC, it does enhance their survival, which may contribute to effects on cycling and numbers of HPC in vivo. Under steady-state conditions, loss of IL-31R on HPC does not appear to influence the activity of competitive repopulating HSC. These results with HPC may be of future utility for manipulation of hematopoiesis in a preclinical setting.
authors: Department of Microbiology and Immunology, and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202-5181, USA. hbroxmey@iupui.edu
authors: Hal E
authors: HE
authors: Broxmeyer
authors: Ji
authors: J
authors: Li
authors: Giao
authors: G
authors: Hangoc
authors: Scott
authors: S
authors: Cooper
authors: Wen
authors: W
authors: Tao
authors: Charlie
authors: C
authors: Mantel
authors: Barbara
authors: B
authors: Graham-Evans
authors: Nico
authors: N
authors: Ghilardi
authors: Frederic J
authors: FJ
authors: de Sauvage
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism*; D042381:Granulocyte Precursor Cells / Q000166:cytology / Q000378:metabolism*; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007378:Interleukins / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000378:metabolism*
chemical_list: C502187:IL31 protein, human; D007378:Interleukins; D018123:Receptors, Interleukin; C502588:interleukin-31, mouse