The motorized RhoGAP myosin IXb (Myo9b) in leukocytes regulates experimental autoimmune encephalomyelitis induction and recovery

J Neuroimmunol. 2015 May 15:282:25-32. doi: 10.1016/j.jneuroim.2015.03.014. Epub 2015 Mar 14.

Abstract

Myo9b regulates leukocyte migration by controlling RhoA signaling. Here we assessed its role in active experimental autoimmune encephalomyelitis (EAE). Myo9b(-/-) mice show a delay in the onset of EAE symptoms. The delay in disease onset was accompanied by reduced numbers of Th1 and Th17 cells in the CNS. Myo9b(-/-) mice showed no recovery from disease symptoms and exhibited elevated numbers of both Th17 cells and CD11b+ macrophages. Bone marrow chimeric mice demonstrated that the absence of a leukocyte source of Myo9b was responsible for the delayed leukocyte infiltration into the CNS, delayed EAE onset and lack of recovery.

Keywords: Bone marrow chimeric mice; Clinical features; Experimental autoimmune encephalomyelitis; Myosin IXb; RhoGAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cell Proliferation / genetics
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Flow Cytometry
  • Gene Expression Regulation / genetics*
  • Image Cytometry
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism
  • Leukocytes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • Myosins / genetics
  • Myosins / metabolism*
  • Peptide Fragments / toxicity
  • Recovery of Function / genetics*
  • Time Factors

Substances

  • Antigens, CD
  • Cytokines
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)
  • myosin IXB
  • Leukocyte Common Antigens
  • Ptprc protein, mouse
  • Myosins