IL-17 producing T cells in mouse models of multiple sclerosis and rheumatoid arthritis

Abstract

Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA) are amongst the most common autoimmune diseases in the northern hemisphere. There is mounting evidence that in both afflictions, not only environmental and genetic factors influence disease, but cellular components such as autoreactive T cells also contribute to pathology. Animal models are key in the study and subsequent therapeutic development for human autoimmune diseases. As patient material is often difficult to obtain and in some cases--as in MS, where the central nervous system (CNS) is concerned--even not accessible, animal models provide a multifaceted tool to explore disease-underlying mechanisms. The pro-inflammatory T cell cytokine IL-17 has recently moved to center stage due to its crucial role in autoimmune diseases including MS and RA. A plethora of studies in animal models has sustained the relevance of this cytokine pathway for the development of autoimmunity and shed light on its cellular sources and patho-mechanisms. This review addresses the role of IL-17 producing T lymphocytes, in particular CD4(+) and γδ T cells, in three commonly used mouse models for MS and RA, namely experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CIA), and antigen-induced arthritis (AIA). Comparing and combining knowledge gained from different animal models will broaden our understanding of the IL-17 biology and facilitate the translation to the human diseases.

Effect of aqueous extract of Achillea millefolium on the development of experimental autoimmune encephalomyelitis in C57BL/6 mice

“…It has been shown that IL-17A has antagonistic effect on the IL-12 and IL-10 secreting cells. Moreover, recent studies demonstrated that IL-17A is one of the main cytokines involved in the induction of the EAE,[25] thus, it is difficult to reconcile the reported influence of IL-17A on EAE with our data that showed no changes in the downstream cytokines, IL-12 and IL-10. Further studies need to clarify possible interaction between these cytokines in EAE-induced mice.…”

Higher susceptibility to experimental autoimmune encephalomyelitis in Muc1-deficient mice is associated with increased Th1/Th17 responses

“…Although EAE was considered to be a Th1-type disease, the discovery of Th17, IL-17 Tγδ, and IL17-producing innate lymphoid cells (ILC17) and the emerging concept of the plasticity of T cell subsets have led to a more complicated picture for T cell involvement in EAE (Petermann and Korn, 2011; Pollinger, 2012). More recently, the distinction between Th1 and Th17 in EAE and in models of colitis has became less distinct, with the discovery that a new type of Th17 cells, which transiently co-express RORγt and T-bet and therefore are IL-17 + IFNγ + , accumulate in the intestine and CNS, respectively (Ahern et al, 2010; Ghoreschi et al, 2010).…”

Expression, Regulation and Function of MicroRNAs in Multiple Sclerosis

“…It has been reported that 7 miRNAs, including miR-16-5p, miR-342-5p, miR-346, miR-518b, miR-760, let-7a-5p and let-7b-5p, were increased, whereas 13 miRNAs, including miR-27a-5p, miR-29a-3p, miR-29b-1-5p, miR-29c-3p, miR-95, miR-149-5p, miR-181c-3p, miR-193a-3p, miR-193-5p, miR-423-5p, miR-532-5p, miR-708-5p and miR-874, were decreased in PBMCs from MS patients after IFN-β therapy 37, which were possibly related with apoptotic processes and IFN feedback loops. In addition, IL-17 was usually up-regulated in MS patients and EAE mice 38. Studies showed that IL-17 suppressed miR-23b expression, which was responsible for the decrease of miR-23b expression in the spinal cords of EAE mice, and in turn, miR-23b down-regulated IL-17 35.…”