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.
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/ IFNg 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.M. , 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.
Segal, B.M. The Role of Natural Killer Cells in Curbing Neuroinflammation. Journal of Neuroimmunology 191(1-2): 2-7, 2007.
Carlson, T., Kroenke, M., Rao, P., Lane, T.E., Segal, B.M. The Th17-ELR+ CXC Chemokine Pathway is Essential for the Development of CNS Autoimmune Disease. Journal of Experimental Medicine 205(4): 811-823, 2008.
Kroenke MA, Carlson TJ, Andjelkovic A, Segal BM. IL-12 and IL-23 modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J Exp Med 2008;205(7): 1535-1541. PMCID: PMC2442630
Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-Gort R, Kasper LH on behalf of the Ustekinumab MS Investigators. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 2008;7(9): 796-804.
Moravan M, Segal BM. Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil. Neurology 2009;72(4): 337-40. PMCID: PMC2677503.
King IL, Dickendesher TL, Segal BM. Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 2009;113(14): 3190-3197. PMCID: PMC2665891.
Segal BM. Getting to the crux of the matter: IL-23 and Th17 cell accumulation in the CNS. Eur J Immunol 2009; 39(7):1713-1715. PMCID: PMC2760599.