Loss of RORγ function in knockout mice and in mice treated with RORγ inverse agonists results in reduced production of proinflammatory cytokines, such as IL-17A/F, and increased resistance to autoimmune disease in several experimental rodent models.
The signaling elicited by the cytokine interleukin-17A (IL-17) is important for antimicrobial defense responses, whereas excessive IL-17 production leads to autoimmune diseases such as psoriasis and multiple sclerosis.
Thus, our findings demonstrate that Bob1 enhances IL-17A expression in vivo and in vitro by interacting with RORγt in Th17 cells, suggesting that Bob1 plays a pivotal role in Th17-mediated autoimmune disease.
Here we briefly review the roles of IL-17 in the pathogenesis of selected autoimmune diseases and provide updates on ongoing and recently completed trials of IL-17 based immunotherapies.
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.
In this report, we provide an overview of studies involving animal models, patient data, genome wide association studies and clinical trials targeting IL-17 for treatment of patients to gain a better understanding of the pathogenic roles of Th17 cells play in a range of autoimmune diseases.
These data support the idea that combined neutralization of TNF-α and IL-17A for refractory autoimmunity is likely to be associated with acceptable and manageable risks of opportunistic infections associated with these cytokines.
Digoxin inhibits RORγt binding to IL-17 and Th17 associated genes, and suppresses IL-17 production in vitro in human and murine leukocytes and in vivo in rodent models of autoimmune disease.
Interleukin-17A (IL-17A)-producing helper T (Th17) cells are a subset of CD4<sup>+</sup> T cells that play important pathological roles in autoimmune diseases.
IL-17-producing CD8<sup>+</sup> (Tc17) cells are enriched in active lesions of patients with multiple sclerosis (MS), suggesting a role in the pathogenesis of autoimmunity.
Development of autoimmunity in smokers with emphysema is also strongly linked to the expansion of autoreactive T helper (Th) cells expressing interferon gamma (Th1), and interleukin 17A (Th17).
Th17 cells are a specialized subset of CD4+ T cells that are essential in driving inflammation during autoimmune disease and infection through a signature cytokine IL-17.
Overall, we show that MHC presentation and the adaptor functions of 14-3-3ζ participate in promoting IFN-γ and IL-17 production, two of the cytokines commonly associated with autoimmune diseases.