title: Emerging role of IL-16 in cytokine-mediated regulation of multiple sclerosis.
abstract: Cytokines are pleiotropic soluble mediators of cellular functions. Cytokines are critical in immune pathogenesis of human diseases, including autoimmune CD4(+) T cell mediated chronic inflammatory, demyelinating and neurodegenerative diseases of the central nervous system (CNS), multiple sclerosis (MS). In MS and its experimental model, experimental autoimmune encephalomyelitis (EAE), chronic persistence and/or reoccurrence of inflammation in the CNS causes chronic progressive or relapsing disease, accompanied with demyelination and damage to axons and oligodendrocytes, which ultimately leads to paralysis and disability. As opposed to other cytokines, whose effects are not limited to the CD4(+) T cell subset, IL-16 exerts its biological properties by exclusive binding and signaling through CD4 receptor. IL-16 selectively regulates migration of all CD4 expressing T cells regardless of their activation state, which is of critical importance for immune modulation and potential therapy of MS. Other major biological properties of IL-16 essential for the function of CD4(+) T cells include regulation of: T cell activation, CD25 expression, MHC class II expression, dendritic cell (DC)-T cell cooperation, B cell-T cell and T cell-T cell cooperation, inflammatory cytokine production and modulation of chemokine regulated T cell chemo-attraction. In this article we outline immune pathogenesis of the disease necessary to understand significance of cytokines and IL-16 in MS regulation. We revisit cytokine regulation with emphasis on involvement of IL-16 mechanisms, implicated in MS progression and important for development of new therapies. We emphasize the significance of similar IL-16 mechanisms for other chronic inflammatory CNS diseases.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA.
authors.forename: Dusanka S
authors.initials: DS
authors.lastname: Skundric
authors.affiliation: Pulmonary Center, Boston University, Boston, MA, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Cruikshank
authors.affiliation: Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Montgomery
authors.affiliation: Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA; Department of Neurology, Wayne State University, Detroit, MI, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Lisak
authors.affiliation: Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA; Department of Neurology, Wayne State University, Detroit, MI, USA. Electronic address: htse@wayne.edu.
authors.forename: Harley Y
authors.initials: HY
authors.lastname: Tse
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001812:Blood-Brain Barrier / Q000276:immunology; D001921:Brain / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D019410:Interleukin-16 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology*
chemical_list: D019410:Interleukin-16
keywords: Cytokines; Experimental autoimmune encephalomyelitis (EAE); Immune pathogenesis; Interleukin-16 (IL-16); Multiple sclerosis (MS)