Title:IL-17A and Multiple Sclerosis: Signaling Pathways, Producing Cells and Target Cells in the Central Nervous System
Volume: 17
Issue: 16
Author(s): Frank Kolbinger, Christine Huppertz, Anis Mir, Franco Di Padova
Affiliation:
关键词:
IL-17、IL17RA IL-17RC
摘要: Multiple sclerosis (MS) is an immune mediated demyelinating disease of
the central nervous system (CNS). The importance of immune cells to MS pathology
is supported by clinical data linking the depletion of T and B cells, or the prevention
of their migration into the brain with significant reduction in relapses and development
of new lesions. In vitro studies, preclinical animal models and encouraging data
with the anti-IL-17A antibody secukinumab in a small proof of concept study in man,
indicate that IL-17A, a key interleukin associated with many inflammatory and autoimmune
diseases, may be involved in MS. Not only cells involved in adaptive immune
responses such as Th17 cells and cytotoxic T cells, or innate immune responses
such as mucosa-associated invariant T (MAIT) cells and γδT cells, but also CNS resident
cells such as astrocytes and oligodendrocytes might contribute to the local production of IL-17A.
IL-17A synergizes with other proinflammatory cytokines, by inducing the release of additional cytokines,
mediators of tissue damage and chemokines, that recruit new inflammatory cells. IL-17A adversely affects
the functions of microglia, astrocytes, oligodendrocytes, neurons, neural precursor cells and endothelial
cells. Blockade of IL-17A might be beneficial to MS patients not only by inhibiting inflammation and tissue
destruction, but also by enhancing repair processes.
