While anti-IL-17 therapies are emerging as an option for psoriasis and other autoimmune disorders, we highlight here a number of questions that would need to be addressed before their potential applicability to treating T1D can be fully evaluated.
Furthermore, the efficacy of IL-17 blockade against other autoimmune diseases, including type 1 diabetes (T1D) is currently unknown and waiting results of ongoing clinical trials.
iNKT cells play different immune function depending on their cytokine-secretion phenotype. iNKT17 cells predominantly secrete IL-17 and have an effector and pathogenic role in the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D).
A significant increase in the levels of interleukin-4 (IL-4), IL-10, and transforming growth factor-β, and a decrease in the levels of IL-17 and interferon-γ in concordance with the significant increase in the Treg cell ratio in splenic MNCs (P < 0.05) was shown in T1DM mice treated with AD-MSC's exosomes as compared to T1DM untreated mice.
In this review we aimed to shed light on the potential role of IL-17 and Th17 cells in both T1D and T2D pathogenesis and future therapeutic strategies.
The expression of IL-17 Receptor A (IL-17RA) in peripheral T lymphocytes and IL-17A serum levels in recent-onset patients with T1D were compared with healthy controls.
Following insulin stimulation, LADA group secreted higher concentration of interleukin-17 (IL-17) (P=0.02) and had higher proportion of interferon gamma (IFN-γ) secretors (P<0.001) than T1DM group.
Proinflammatory cytokines such as IL-1<i>β</i>, IL-6, TNF-<i>α</i>, IFN-<i>γ</i>, IL-12, IL-17, and NO can be released by CD4 and CD8<sup>+</sup> lymphocytes as well as by classically activated macrophages (CAM<i>ϕ</i>s), which are important in the development of T1D.
In conclusion, IFN-γ, IL-12 and IL-17 played an essential role in exacerbating EV<sup>+</sup> -T1D, while C3d, sC5b -9, IL-10 and -20 displayed distinct patterns.
IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes.
However, the Treg cells showed a decreased production of anti-inflammatory (IL-10, IL-35, TGF-β) and increased pro-inflammatory (IFN-γ, IL-2, IL-17) cytokines, indicating a phenotypic shift of Treg cells under T1D condition.
The potent contributions of CD27(-) γδ T cells and IL-17 to islet inflammation and diabetes reported in this study suggest that these mechanisms may also underlie human T1D.
Given the Th17 immunity in T1D, we demonstrated that IL-17 had detrimental effects on human islet cells in vitro; it potentiated both inflammatory and proapoptotic responses.