Microglia and Dendritic Cells as a Source of IL-6 in a Mouse Model of Multiple Sclerosis

Biochemistry (Mosc). 2024 May;89(5):904-911. doi: 10.1134/S0006297924050109.


Multiple sclerosis (MS) is a complex autoimmune disease of central nervous system (CNS) characterized by the myelin sheath destruction and compromised nerve signal transmission. Understanding molecular mechanisms driving MS development is critical due to its early onset, chronic course, and therapeutic approaches based only on symptomatic treatment. Cytokines are known to play a pivotal role in the MS pathogenesis with interleukin-6 (IL-6) being one of the key mediators. This study investigates contribution of IL-6 produced by microglia and dendritic cells to the development of experimental autoimmune encephalomyelitis (EAE), a widely used mouse model of MS. Mice with conditional inactivation of IL-6 in the CX3CR1+ cells, including microglia, or CD11c+ dendritic cells, displayed less severe symptoms as compared to their wild-type counterparts. Mice with microglial IL-6 deletion exhibited an elevated proportion of regulatory T cells and reduced percentage of pathogenic IFNγ-producing CD4+ T cells, accompanied by the decrease in pro-inflammatory monocytes in the CNS at the peak of EAE. At the same time, deletion of IL-6 from microglia resulted in the increase of CCR6+ T cells and GM-CSF-producing T cells. Conversely, mice with IL-6 deficiency in the dendritic cells showed not only the previously described increase in the proportion of regulatory T cells and decrease in the proportion of TH17 cells, but also reduction in the production of GM-CSF and IFNγ in the secondary lymphoid organs. In summary, IL-6 functions during EAE depend on both the source and localization of immune response: the microglial IL-6 exerts both pathogenic and protective functions specifically in the CNS, whereas the dendritic cell-derived IL-6, in addition to being critically involved in the balance of regulatory T cells and TH17 cells, may stimulate production of cytokines associated with pathogenic functions of T cells.

Keywords: dendritic cells; experimental autoimmune encephalomyelitis; interleukin-6; microglia; mouse models; multiple sclerosis.

MeSH terms

  • Animals
  • CX3C Chemokine Receptor 1 / genetics
  • CX3C Chemokine Receptor 1 / metabolism
  • Dendritic Cells* / immunology
  • Dendritic Cells* / metabolism
  • Disease Models, Animal*
  • Encephalomyelitis, Autoimmune, Experimental* / immunology
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Encephalomyelitis, Autoimmune, Experimental* / pathology
  • Female
  • Interleukin-6* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microglia* / metabolism
  • Multiple Sclerosis* / immunology
  • Multiple Sclerosis* / metabolism
  • Multiple Sclerosis* / pathology
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism


  • Interleukin-6
  • interleukin-6, mouse
  • CX3C Chemokine Receptor 1
  • Receptors, CCR6