The role of IL-17 in CNS diseases

Abstract

Cytokines of the IL-17 family are uniquely placed on the border between immune cells and tissue. Although IL-17 was originally found to induce the activation and mobilization of neutrophils to sites of inflammation, its tissue-specific function is not yet fully understood. The best-studied IL-17 family members, IL-17A and IL-17F, are both typically produced by immune cells such as Th17, γδ T cells and innate lymphoid cells group 3. However, the cells that respond to these cytokines are mostly found in inflamed tissue. As seen in psoriatic skin lesions or in joints of rheumatoid arthritis patients, high levels of IL-17 have been detected in the central nervous system (CNS) during inflammatory responses. Here, we provide a general review of the molecular function of IL-17 and its role in the CNS in particular. Of the different inflammatory conditions of the CNS, we found multiple sclerosis (MS) to be the one most associated with the presence of Th17 cells and IL-17. In particular, many studies using the murine model for MS, experimental autoimmune encephalomyelitis, found a clear association of Th17 and IL-17 with disease severity and progression. We summarize the recent advances made in correlating the presence of IL-17 with impaired blood-brain barrier integrity as well as the activation of astrocytes and microglia and the consequences for disease progression. There is also evidence that IL-17 plays a pathogenic role in the post-ischemic phase of stroke as well as its experimental model. We review the limited but promising data on the sources of post-stroke IL-17 production and its effects on CNS-resident target cells. In addition to MS and stroke, there is also evidence linking high levels of IL-17 to depression, as a frequent comorbidity of several inflammatory diseases, as well as to different types of infections of the CNS. The evidence we supply here suggests that inhibiting the function of the IL-17 cytokine family could have a beneficial effect on pathogenic conditions in the CNS.

Chemokines and chemokine receptors in the pathogenesis of multiple sclerosis

“…Tumor Necrosing Factor, TNF-α). Takođe, IL-17 može, sam ili u sinergiji s drugim molekularnim faktorima, da prouzrokuje oštećenje neurona (12).…”

The inflammatory perspective of depression in the context of chronic medical conditions

“…Furthermore, mice lacking RORγt, the transcription factor essential for Th17 cell development, were less prone to develop depression [10]. This probably indicates that Th17 cells have the capacity to directly affect target cells in the CNS, possibly through IL-17 (for review see The role of IL-17 in CNS diseases [11]). …”

T Cell-Derived GM-CSF, Regulation of Expression and Function

“…The TH17 cells are believed to play important roles in various inflammatory and autoimmune diseases including MS and rheumatoid arthritis (RA) [10,11]. However, the main cytokines produced by TH17 cells were found to be nonessential in EAE.…”