IL-17 Plays an Important Role in the Development of Experimental Autoimmune Encephalomyelitis

Abstract

IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17−/− murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17−/− mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17−/− mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of IL-17−/− CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL-17-producing T cells were increased in IFN-γ−/− cells, while IFN-γ-producing cells were increased in IL-17−/− cells, suggesting that IL-17 and IFN-γ mutually regulate IFN-γ and IL-17 production. These observations indicate that IL-17 rather than IFN-γ plays a crucial role in the development of EAE.

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

“…Il17 –/– mice show significantly reduced severity in various inflammatory and autoimmune disease models, such as collagen‐induced arthritis,6 Il1rn −/− mouse arthritis,7 EAE8 and imiquimod (IMQ)‐induced skin inflammation,9, 10 suggesting critical roles of IL‐17 in inflammatory/autoimmune diseases. γδ 17 cells are detected in inflamed tissues of these disease models.…”

“…Mice deficient for IL‐17RA are highly susceptible to Klebsiella pneumoniae 3 and IL‐17‐deficient mice are susceptible to bacterial and fungal infection 4, 5. Interleukin‐17 is also implicated in various inflammatory/autoimmune disease models such as experimental autoimmune encephalomyelitis (EAE), arthritis in IL‐1 receptor antagonist‐deficient (Il1rn –/– ) mice and imiquimod‐induced psoriatic dermatitis in mice 6, 7, 8, 9, 10. Anti‐IL‐17 and anti‐IL‐17RA antibodies are effective to treat patients with psoriasis and psoriatic arthritis 11, 12, 13.…”

CCL2 recruitment of IL‐6‐producing CD11b+ monocytes to the draining lymph nodes during the initiation of Th17‐dependent B cell‐mediated autoimmunity

“…Helper CD4 + T cells that are characterized by the production of IL-17 are commonly called Th17 cells [1][2][3][4][5][6]. Th17 cells have features that are distinct from those of both Th1 and Th2 lineages.…”

“…Th17 cells have features that are distinct from those of both Th1 and Th2 lineages. For example, TGF-b and IL-6 are required for the generation of Th17 cells, and IL-23 supports the survival and expansion of these cells [1][2][3][4][5][6][7][8]. Recent data also suggest that IL-6 and TGF-b drive initial lineage commitment of Th17 cells, whereas IL-23 mediates the full acquisition of pathogenic function of Th17 cells [9].…”

Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with multiple sclerosis

“…autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), a murine model of MS (Komiyama et al, 2006). Previous MS studies have also demonstrated increased amounts of IL-12p40 in the nervous system and increased IL-12 production by PBMC (Balashov et al, 1997;Comabella et al, 1998;Soldan et al, 2004).…”