IL-10 enhances the phenotype of M2 macrophages induced by IL-4 and confers the ability to increase eosinophil migration

Int Immunol. 2015 Mar;27(3):131-41. doi: 10.1093/intimm/dxu090. Epub 2014 Sep 29.


M2 macrophages have been subdivided into subtypes such as IL-4-induced M2a and IL-10-induced M2c in vitro. Although it was reported that IL-10 stimulation leads to an increase in IL-4Rα, the effect of IL-4 and IL-10 in combination with macrophage subtype differentiation remains unclear. Thus, we sought to clarify whether IL-10 enhanced the M2 phenotype induced by IL-4. In this study, we showed that IL-10 enhanced IL-4Rα expression in M-CSF-induced bone marrow-derived macrophages (BMDMs). Global gene expression analysis of M2 macrophages induced by IL-4, IL-10 or IL-4 + IL-10 showed that IL-10 enhanced gene expression of M2a markers induced by IL-4 in M-CSF-induced BMDMs. Moreover, IL-4 and IL-10 synergistically induced CCL24 (Eotaxin-2) production. Enhanced CCL24 expression was also observed in GM-CSF-induced BMDMs and zymosan-elicited, thioglycolate-elicited and naive peritoneal macrophages. CCL24 is a CCR3 agonist and an eosinophil chemoattractant. In vitro, IL-4 + IL-10-stimulated macrophages produced a large amount of CCL24 and increased eosinophil migration, which was inhibited by anti-CCL24 antibody. We also showed that IL-4 + IL-10-stimulated (but not IL-4 or IL-10 alone) macrophages transferred into the peritoneum of C57BL/6J mice increased eosinophil infiltration into the peritoneal cavity. These results demonstrate that IL-4 + IL-10-simulated macrophages have enhanced M2a macrophage-related gene expression, CCL24 production and eosinophil infiltration-inducing activity, thereby suggesting their contribution to eosinophil-related diseases.

Keywords: CCL24; IL-10; IL-4; M2a macrophage; eosinophil infiltration.

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Cell Differentiation
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chemokine CCL4 / genetics
  • Chemokine CCL4 / metabolism*
  • Eosinophils / immunology*
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism*
  • Macrophage Colony-Stimulating Factor / immunology
  • Macrophages / immunology*
  • Macrophages / transplantation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microarray Analysis
  • Phenotype
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Up-Regulation


  • Antibodies, Blocking
  • Chemokine CCL4
  • Il4ra protein, mouse
  • Receptors, Cell Surface
  • Interleukin-10
  • Interleukin-4
  • Macrophage Colony-Stimulating Factor