John H. Russell, Ph.D.

Developmental Biology

General Program

  • 314-362-2558

  • 314-362-2559

  • 314-362-7058

  • 8103

  • 305 McDonnell Medical Sciences Building



  • apoptosis, autoimmunity, imaging, inflammation, multiple sclerosis

  • CNS/lymphocyte interactions regulating inflammation and pathogenesis in a mouse model of multiple sclerosis

Research Abstract:

Research in this laboratory focuses on CNS (brain and spinal cord) inflammation and pathogenesis in a mouse model of multiple sclerosis. We have used genetically marked lymphocytes to study the mechanisms of their entry into the CNS to cause disease. We have found that the initial compromise of the blood brain barrier requires that lymphocytes “see” a CNS antigen in the space between blood vessels and the parenchyma (body) of the CNS. This interaction initiates a “conversation” between cells originating in the blood and cells of the parenchyma itself that determines whether or not inflammatory invasion will occur.

The molecular language of this “conversation” is a group of small proteins (cytokines and chemokines) that regulate the expression of adhesion molecules (VCAM-1) on astrocytes in the parenchyma and recruit macrophages and other inflammatory cells. The VCAM-1 expression on astrocytes appears to be an important mechanism to allow both the recruitment and retention of the inflammatory infiltrate into the parenchyma, causing demyelination and axon loss associated with paralysis.

We have developed a novel technique to isolate the infiltrating lymphocytes at various stages of invasion. Current experiments are focused on understanding the molecular changes in the lymphocytes as they invade the CNS to identify possible targets for preventing their invasion of the CNS. We are also focusing on the role of the astrocyte in both promoting and protecting from or healing the inflammatory process. Our results suggest that there may be regionally specific “dialects” of the conversation making some CNS regions more susceptible to invasion than others and astrocytes are an important part of those regional differences.

Selected Publications:

Archambault AS, Sim J, McCandless EE, Klein RS, Russell JH. Region-specific regulation of inflammation and pathogenesis in experimental autoimmune encephalomyelitis. J Neuroimmunol 2006 181:122-132.

Gimenez MA, Sim J, Archambault AS, Klein RS, Russell JH. A TNFR1-dependent conversation between CNS-specific T cells and the CNS is required for inflammatory infiltration of the spinal cord. Am J Pathol 2006 168:1200-1209.

Lees JR, Archambault AS, Russell JH. T-cell trafficking competence is required for CNS invasion. J Neuroimmunol 2006 177:1-10.

Archambault AS, Sim, J Gimenez MA, Russell JH. Defining Antigen Dependent Stages of T cell Migration from the Blood to the Central Nervous System Parenchyma. Eur J Immunol 2005 35:1076-1085.

Gimenez MA., Sim J, Russell JH. TNFR1-Dependent Parenchymal VCAM-1 Expression Lays Down the Path for Destructive CNS Inflammation. J Neuroimmunol 2004 151:116-125.

Last Updated: 8/6/2013 9:58:04 AM

Back To Top

Follow us: