Benjamin Segal, M.D.
Holtom-Garrett Professor of Neurology
Chief, Holtom-Garrett Multiple Sclerosis Center and Neuroimmunology Laboratory

bmsegal@umich.edu


Our research investigates how chemokine and cytokine networks and leukocyte subsets act together, both in peripheral lymphoid tissues and the central nervous system (CNS), to mediate autoimmune diseases that target neuronal or glial antigens normally sequestered behind the blood-brain-barrier . We are particularly interested in the inflammatory demyelinating disease, multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) . One part of the lab oratory is devoted to human immunological studies (involving the analysis of peripheral blood and cerebrospinal fluid mononuclear cells that are collected from patients with MS or other neurological diseases and healthy controls) . Currently we are investigating the relationship between the expression of selected cytokines (such as IL-23 and IL-17) and disease activity, as detected by advanced MRI techniques, in individuals with progressive multiple scleroris . A complimentary division of our lab is dedicated to animals studies, primarily using the EAE model .

Some of our on-going projects are to investigate the following: (i) the expression pattern and role of the interleukin (IL)-12 p40 family of monokines in secondary progressive MS; (ii) the role of IL-12 and IL-23 in T cell homing to the CNS and epitope spreading during the course of EAE; (iii) CNS expression and functional significance of “lymphoid” chemokines, such as CXCL13 and CCL21, in driving the formation of organized inflammatory infiltrates during relapsing EAE and MS; (iv) the origin and biological activities of dendritic cells that accumulate in demyelinating lesions during EAE; (v) the importance of regulatory T cells for remission during relapsing autoimmune demyelination; (vi) the role of neutrophils and the chemokines that attract them in blood-brain-barrier breakdown during EAE; and (vii) the impact of b -IFN therapy on the immune system of patients with MS .

Representative Publications

Segal, B.M. , Dwyer, B., Shevach, E.M. An IL-12/IL-10 Immunoregulatory Circuit Controls Susceptibility to Autoimmune Disease. Journal of Experimental Medicine 187: 537-546, 1998.

Segal, B.M. The comeback of the elusive “suppressor” cell: An update on the regulatory network in EAE. Research in immunology 149: 811-820, 1998.

Chang, J.T., Shevach, E.M., Segal, B.M. Regulation of IL-12 Receptor ß2 Subunit Expression by Endogenous IL-12: A Critical Step in the Differentiation of Pathogenic Autoreactive T cells. Journal of Experimental Medicine 189: 969-978, 1999.

Segal, B.M., Chang, J.T., Shevach, E.M. CpG Oligonucleotides are Potent Adjuvants for the Activation of Autoreactive Encephalitogenic T Cells in Vivo. Journal of Immunology 164: 5683-5688, 2000.

Segal, B.M. , Glass, D. and Shevach, E.M. IL-10 Producing Tr1 Cells Mediate Tumor Rejection, Journal of Immunology (Cutting Edge) 168: 1-4, 2002.

Ichikawa , H., Williams, L.P. and Segal, B.M. Activation of Antigen Presenting Cells through CD40 or Toll-9 Receptors Overcomes Tolerance and Precipitates Autoimmune Disease. Journal of Immunology, 169:2781-2787 2002.

Schwid S.R., Covington M., Segal B.M. and Goodman A.D.: Fatigue in multiple sclerosis: current understanding and future directions. Journal of Rehabilitation Research and Development 39(2): 211-224, 2002.

Segal, B.M. Experimental Autoimmune Encephalomyelitis: Cytokines, Antigen Presenting Cells and Immunoregulation. Current Allergy and Asthma Reports 3(1): 86-93, 2003.

Bagaeva, L . , Williams, L . P . and Segal, B . M . : IL-12 Dependent/ IFN g Independent Expression of CCR5 by Myelin Reactive T Cells Correlates with Encephalitogenicity . Journal of Neuroimmunology 137(1-2): 109-116, 2003 .

Rao, P . and Segal, B . M . Experimental Autoimmune Encephalomyelitis . Methods Mol . Med . 102: 363-376, 2004 .

Segal, B.M. CNS chemokines, cytokines, and dendritic cells in autoimmune demyelination. J Neurol Sci. 228(2):210-4, 2005.

Sha, S. , Divekar, A. A., Hilchey, S. P., Cho, H.M., Newman, C.L., Shin, S. U., Nechustan, H., Challita-Eid, P.M., Segal, B.., Yi, K.H., and Rosenblatt, J.D. Increased rejection of primary tumors in mice lacking B cells: Inhibition of anti-tumor CTL and T(H)1 cytokine responses by B cells. Int. J . Cancer 117(4): 574-86, 2005.

Segal, B.M. and Logigan E . L . Sublime diagnosis of Lyme neuroboreliosis. Neurology 65(3): 351-2, 2005.

King, I . and Segal, B.M. Cutting Edge: IL-12 induces CD4 + CD25 - T cell activation in the presence of regulatory T cells. Journal of Immunology (Cutting Edge section) 175(2): 641-5, 2005.

Deshpande, P . and Segal, B.M. IL-12 driven upregulation of P-selectin ligand on myelin-specific T cells is a critical step in an animal model of autoimmune demyelination. Journal of Neuroimmunology 173(1-2):35-44, 2006 .

Bagaeva, L . V . , Rao, P . , Powers, J . M . and Segal, B.M. CXCL13 plays a role in experimental autoimmune encephalomyelitis. Journal of Immunology. 176(12):7676-85, 2006.

Kroenke, M . A . and Segal, B.M . Th17 and Th1 responses directed against the immunizing epitope, as opposed to secondary epitopes, dominate the autoimmune repertoire during relapses of experimental autoimmune encephalomyelitis . Journal of Neuroscience Research . 85(8):1685-93, 2007 .

Deshpande, P . , King, I,L . and Segal, B.M. Cutting Edge: CNS CD11c + cells from mice with encephalomyelitis polarize Th17 cells and support CD25 + CD4 + mediated immunosuppression, suggesting dual roles in the disease process . Journal of Immunology. 178(11): 6695-99, 2007.