title: IL-3 and CSF-1 interact to promote generation of CD11c+ IL-10-producing macrophages.
abstract: Unraveling the mechanisms of hematopoiesis regulated by multiple cytokines remains a challenge in hematology. IL-3 is an allergic cytokine with the multilineage potential, while CSF-1 is produced in the steady state with restricted lineage coverage. Here, we uncovered an instructive role of CSF-1 in IL-3-mediated hematopoiesis. CSF-1 significantly promoted IL-3-driven CD11c+ cell expansion and dampened basophil and mast cell generation from C57BL/6 bone marrow. Further studies indicated that the CSF-1/CSF-1R axis contributed significantly to IL-3-induced CD11c+ cell generation through enhancing c-Fos-associated monopoiesis. CD11c+ cells induced by IL-3 or IL-3/CSF-1 were competent in cellular maturation and endocytosis. Both IL-3 and IL-3/CSF-1 cells lacked classical dendritic cell appearance and resembled macrophages in morphology. Both populations produced a high level of IL-10, in addition to IL-1, IL-6 and TNFα, in response to LPS, and were relatively poor T cell stimulators. Collectively, these findings reveal a role for CSF-1 in mediating the IL-3 hematopoietic pathway through monopoiesis, which regulates expansion of CD11c+ macrophages.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, Australia.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Sheng
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, Australia.
authors.forename: Lara J
authors.initials: LJ
authors.lastname: Herrero
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Division of Molecular Medicine, The John Curtin School of Medical Research, The Australian National University, ACT, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hapel
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, Australia.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D007377:Interleukin-3 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D038042:Myelopoiesis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D039521:CD11c Antigen; C556062:IL10 protein, mouse; D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor
references.citation: Int Immunol. 2008 Sep;20(9):1201-9
references.pmid: 18632726
references.citation: Blood. 2008 Jan 1;111(1):150-9
references.pmid: 17916748
references.citation: Eur J Immunol. 1996 Jun;26(6):1388-93
references.pmid: 8647221
references.citation: Blood. 2003 Feb 1;101(3):1155-63
references.pmid: 12393599
references.citation: Nature. 1986 Nov 6-12;324(6092):65-7
references.pmid: 3491321
references.citation: Oncogene. 2000 May 15;19(21):2532-47
references.pmid: 10851052
references.citation: Nat Rev Immunol. 2011 Oct 14;11(11):723-37
references.pmid: 21997792
references.citation: Mol Reprod Dev. 1997 Jan;46(1):4-10
references.pmid: 8981357
references.citation: Nature. 2013 May 9;497(7448):239-43
references.pmid: 23575636
references.citation: J Invest Dermatol. 2003 Aug;121(2):280-8
references.pmid: 12880419
references.citation: Blood. 1991 May 15;77(10):2118-21
references.pmid: 1903073
references.citation: Nature. 1998 Mar 5;392(6671):90-3
references.pmid: 9510253
references.citation: Immunity. 2012 Jun 29;36(6):1031-46
references.pmid: 22749353
references.citation: Blood. 2011 Aug 25;118(8):2266-74
references.pmid: 21725048
references.citation: Immunol Ser. 1990;49:177-214
references.pmid: 2090251
references.citation: Br J Haematol. 1990 Feb;74(2):131-7
references.pmid: 2138495
references.citation: Blood. 1985 Jun;65(6):1453-9
references.pmid: 3922456
references.citation: J Cell Physiol. 1985 Mar;122(3):362-9
references.pmid: 2981895
references.citation: Curr Opin Immunol. 2006 Feb;18(1):39-48
references.pmid: 16337366
references.citation: Blood. 1996 Mar 15;87(6):2376-85
references.pmid: 8630401
references.citation: J Immunol. 2008 Aug 15;181(4):2455-64
references.pmid: 18684936
references.citation: Blood. 2009 Sep 3;114(10):2172-80
references.pmid: 19587381
references.citation: Nature. 1989 May 4;339(6219):64-7
references.pmid: 2469965
references.citation: Blood. 1986 Jul;68(1):46-57
references.pmid: 3087441
references.citation: Br J Haematol. 1990 Feb;74(2):138-45
references.pmid: 2180468
references.citation: J Immunol. 2012 Apr 15;188(8):3603-10
references.pmid: 22442444
references.citation: Blood. 2002 Feb 1;99(3):993-8
references.pmid: 11807004
references.citation: Cell Growth Differ. 1991 Jun;2(6):267-72
references.pmid: 1712226
references.citation: Blood. 1989 Mar;73(4):945-51
references.pmid: 2645952
references.citation: J Immunol. 2002 Jun 15;168(12):6199-207
references.pmid: 12055233
references.citation: Oncogene. 1995 Dec 21;11(12):2469-76
references.pmid: 8545103