Targeting Th17 cells in CNS immune pathology
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mediated by autoreactive T lymphocytes. A new class of CD4+ T cells, the Th17 lineage, has recently been described and has been implicated in initiating immune responses against CNS autoantigens. Findings in experimental autoimmune encephalomyelitis (EAE, the animal model for MS) suggest that targeting Th17 cells may have a beneficial outcome for patients suffering from MS. Several existing and emerging therapeutic strategies are discussed based on the manner in which they target Th17-mediated autoimmunity: lymphocyte depletion, prevention of Th17 development, and prevention of Th17 function. T cell-ablating agents are not Th17 specific and are associated with toxicity and opportunistic infections. The prevention of Th17 differentiation can be achieved experimentally by neutralizing cytokines required for Th17 development and by the administration of cytokines or other chemicals that interfere with differentiation; however, these strategies may also lead to disease. Prevention of functional Th17 responses can be accomplished by inhibiting leukocyte trafficking or by neutralizing IL-17. While several promising therapeutic candidates have been identified using EAE and clinical experimentation, both the risks of immunomodulation as well as the efficacy of such candidates in human patients need to be completely characterized and carefully considered.
KeywordsMultiple Sclerosis Th17 Cell Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Patient Glatiramer Acetate
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