title: The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE.
abstract: BACKGROUND
  Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate immune system has been proposed, based e.g. on the observation that innate immune receptors modulate disease severity of experimental autoimmune encephalomyelitis. Recent studies of our group provided first evidence for a key role of the innate immune LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice showed increased clinical symptoms and enhanced infiltration of monocytes and neutrophils in brain and spinal cord.
  
  
  METHODS
  In the current study, we further investigated the causes of the disease aggravation by CD14-deficiency and examined T cell activation, also focusing on the costimulatory molecules CTLA-4 and CD28, and T cell migration capacity over the blood brain barrier by FACS analysis, in vitro adhesion and transmigration assays.
  
  
  RESULTS
  In the results, we observed a significantly increased migration of CD14-deficient lymphocytes across an endothelial monolayer. In contrast, we did not see any differences in expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to endothelial cells from CD14-deficient compared to wildtype mice.
  
  
  CONCLUSIONS
  The results demonstrate an important role of CD14 in migration of lymphocytes, and strengthen the importance of innate immune receptors in adaptive immune disorders, such as multiple sclerosis.
authors: Department of Neurology, Saarland University Hospital, Homburg, Germany.
authors: Ramona
authors: R
authors: Halmer
authors: Laura
authors: L
authors: Davies
authors: Yang
authors: Y
authors: Liu
authors: Klaus
authors: K
authors: Fassbender
authors: Silke
authors: S
authors: Walter
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D060908:CTLA-4 Antigen / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D011971:Receptors, Immunologic / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D018950:Lipopolysaccharide Receptors; D011971:Receptors, Immunologic