Chronic inflammatory diseases (CID) are a spectrum of clinically heterogeneous conditions that share aspects of the same immune-mediated pathogenic mechanisms. These disorders affect around 7% of the population and impose a considerable burden on the society, because of the elevated costs of treatment. The introduction of biological therapies targeting specific pro-inflammatory cytokines has revolutionized the treatment of CID, although responses remain unpredictable in a considerable number of patients. Genome-wide association studies (GWAS) together with pre-clinical studies in mouse models of autoimmune diseases, indicated that the IL-23/IL-17 axis plays a pivotal role in the initiation of inflammatory diseases. Several of the identified loci are associated with multiple CIDs, such as Crohn’s disease, psoriasis, and axial spondyloarthritis (axSpA), suggesting an overlap of pathogenic mechanisms among different disease conditions. Interleukin 23 (IL-23) is important for the expansion and the functional activity of the pro-inflammatory CD4+ T cell subset (Th17), which secretes IL-17. Mouse models of autoimmune disease have highlighted the role of IL-23 and of antigen-specific Th17 cells in sustaining autoimmune inflammation. However, several studies have suggested that IL-23 may also regulate the function of additional immune cell populations, which are capable of secreting IL-17 and may be involved in the pathogenesis of immune-mediated diseases, including Innate lymphoid cells (ILCs), ?d T lymphocytes, iNKT cells, mucosal-associated invariant T cells (MAIT), and, possibly, neutrophils. Some of these populations have been found to accumulate in the diseased tissues of patients or of model animals, suggesting that the inflammatory response in CID may be the result of a complex interplay of different immune cell types affected by IL-23/IL-17 signaling.
The implication of the IL-23/IL-17 axis has also been clinically validated by the successful treatment of selected CID with biological inhibitors of IL-17 or IL-23. However, the clinical studies using these drugs have also given unexpected results, dissociating the effectiveness of IL-17 from IL-23 inhibitors in different diseases. In fact, IL-17A blockers are effective in the treatment of axSpA, psoriasis, and psoriatic arthritis (a disease of the SpA spectrum), but induce worsening of symptoms in Crohn’ s disease. Conversely, targeting IL-23 has proven effective for the treatment of psoriasis and Crohn’s disease, but failed in patients with axSpA. These findings demonstrate our limited understanding of the pathogenic mechanisms of these diseases, as well as of the mechanism of actions of the IL-17 and IL-23 inhibitors tested so far, thus suggesting the need to carefully reassess the link between IL-23 and IL-17 in CID.
This Research Topic will give a comprehensive overview about the impact of the IL-23/IL-17 pathways in chronic immune-mediated inflammatory diseases, with particular emphasis on the molecular mechanisms driving pathogenesis and response to therapy. The themes addressed by this Research Topic will include, but are not limited to, the followings:
• IL-17 producing cell subsets in health and disease, with a focus on SpA, psoriasis, psoriatic arthritis, inflammatory bowel disease (IBD)
• The IL-23/IL-17 pathway and microbiota in the pathogenesis of CID
• Human monogenic mutations and genetics variants of the IL-23/IL-17 axis
• Inhibition of the IL-23/IL-17 pathway in human chronic inflammatory diseases (focus on SpA, psoriasis, psoriatic arthritis, IBD), including novel therapeutic approaches
We welcome the submission of Original Research, Reviews, Mini-reviews and Perspective articles.
Topic Editor Dr. Rogge recieved the Sanofi Innovation Award Europe to finance a project on: Defining the mechanisms of action of biologic therapies in spondyloarthritis.
The other Topic Editors declare no conflict of interest with regard to the Research Topic theme.
Chronic inflammatory diseases (CID) are a spectrum of clinically heterogeneous conditions that share aspects of the same immune-mediated pathogenic mechanisms. These disorders affect around 7% of the population and impose a considerable burden on the society, because of the elevated costs of treatment. The introduction of biological therapies targeting specific pro-inflammatory cytokines has revolutionized the treatment of CID, although responses remain unpredictable in a considerable number of patients. Genome-wide association studies (GWAS) together with pre-clinical studies in mouse models of autoimmune diseases, indicated that the IL-23/IL-17 axis plays a pivotal role in the initiation of inflammatory diseases. Several of the identified loci are associated with multiple CIDs, such as Crohn’s disease, psoriasis, and axial spondyloarthritis (axSpA), suggesting an overlap of pathogenic mechanisms among different disease conditions. Interleukin 23 (IL-23) is important for the expansion and the functional activity of the pro-inflammatory CD4+ T cell subset (Th17), which secretes IL-17. Mouse models of autoimmune disease have highlighted the role of IL-23 and of antigen-specific Th17 cells in sustaining autoimmune inflammation. However, several studies have suggested that IL-23 may also regulate the function of additional immune cell populations, which are capable of secreting IL-17 and may be involved in the pathogenesis of immune-mediated diseases, including Innate lymphoid cells (ILCs), ?d T lymphocytes, iNKT cells, mucosal-associated invariant T cells (MAIT), and, possibly, neutrophils. Some of these populations have been found to accumulate in the diseased tissues of patients or of model animals, suggesting that the inflammatory response in CID may be the result of a complex interplay of different immune cell types affected by IL-23/IL-17 signaling.
The implication of the IL-23/IL-17 axis has also been clinically validated by the successful treatment of selected CID with biological inhibitors of IL-17 or IL-23. However, the clinical studies using these drugs have also given unexpected results, dissociating the effectiveness of IL-17 from IL-23 inhibitors in different diseases. In fact, IL-17A blockers are effective in the treatment of axSpA, psoriasis, and psoriatic arthritis (a disease of the SpA spectrum), but induce worsening of symptoms in Crohn’ s disease. Conversely, targeting IL-23 has proven effective for the treatment of psoriasis and Crohn’s disease, but failed in patients with axSpA. These findings demonstrate our limited understanding of the pathogenic mechanisms of these diseases, as well as of the mechanism of actions of the IL-17 and IL-23 inhibitors tested so far, thus suggesting the need to carefully reassess the link between IL-23 and IL-17 in CID.
This Research Topic will give a comprehensive overview about the impact of the IL-23/IL-17 pathways in chronic immune-mediated inflammatory diseases, with particular emphasis on the molecular mechanisms driving pathogenesis and response to therapy. The themes addressed by this Research Topic will include, but are not limited to, the followings:
• IL-17 producing cell subsets in health and disease, with a focus on SpA, psoriasis, psoriatic arthritis, inflammatory bowel disease (IBD)
• The IL-23/IL-17 pathway and microbiota in the pathogenesis of CID
• Human monogenic mutations and genetics variants of the IL-23/IL-17 axis
• Inhibition of the IL-23/IL-17 pathway in human chronic inflammatory diseases (focus on SpA, psoriasis, psoriatic arthritis, IBD), including novel therapeutic approaches
We welcome the submission of Original Research, Reviews, Mini-reviews and Perspective articles.
Topic Editor Dr. Rogge recieved the Sanofi Innovation Award Europe to finance a project on: Defining the mechanisms of action of biologic therapies in spondyloarthritis.
The other Topic Editors declare no conflict of interest with regard to the Research Topic theme.
