Toll-Like Receptor 4 Promotes Th17 Lymphocyte Infiltration Via CCL25/CCR9 in Pathogenesis of Experimental Autoimmune Encephalomyelitis

J Neuroimmune Pharmacol. 2019 Sep;14(3):493-502. doi: 10.1007/s11481-019-09854-1. Epub 2019 May 8.

Abstract

Toll-like receptor 4 (TLR4) is a key component in innate immunity and has been linked to central nervous system (CNS) inflammation diseases, such as multiple sclerosis (MS), an inflammatory disorder induced by autoreactive Th17 cells. In our study, we found that TLR4 deficient (TLR4-/-) mice were inadequate to induce experimental autoimmune encephalomyelitis (EAE), characterized by low clinic score and weight loss, alleviative demyelinating, as well as decreased inflammatory cell infiltration in the spinal cord. In the lesion area of EAE mice, loss of TLR4 down-regulated the secretion of inflammatory cytokines and chemokine CCL25. Furthermore, the expression of CCR9 was decreased and chemotactic migration was attenuated in TLR4-/- Th17 cells. Our results demonstrate that TLR4 may mediate Th17 infiltration through CCL25/CCR9 signal during pathogenesis of EAE. Graphical Abstract Immunofluorescent staining of RORγt (green) and CCR9 (red) in spinal cords. TLR4 deficiency down-regulates CCR9 expression in infiltrating lymphocytes.

Keywords: CCL25/CCR9; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Th17 cells; Toll-like receptor 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokines, CC / physiology*
  • Chemotaxis, Leukocyte
  • Encephalomyelitis, Autoimmune, Experimental / etiology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Gene Expression Regulation / physiology
  • Lymphopoiesis
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • Peptide Fragments / immunology
  • Peptide Fragments / toxicity
  • Receptors, CCR / biosynthesis
  • Receptors, CCR / physiology*
  • Signal Transduction / physiology
  • Spinal Cord / pathology
  • Spleen / immunology
  • Spleen / pathology
  • Th17 Cells / metabolism*
  • Toll-Like Receptor 4 / deficiency
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / physiology*

Substances

  • CC chemokine receptor 9
  • Ccl25 protein, mouse
  • Chemokines, CC
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, CCR
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • myelin oligodendrocyte glycoprotein (35-55)