Cellular sources of IL‐17 in psoriasis: a paradigm shift?

Abstract

Psoriasis is a common chronic inflammatory skin disease that results from interplay between the immune system and the epithelium. In the light of very successful anticytokine therapies for psoriasis, the focus has been directed towards the adaptive immune system. Expression studies, genetic studies and treatments specifically targeting players of the IL-23/IL-17 pathway, point at an important role for IL-17 in the pathogenesis of psoriasis. IL-17 stimulates the keratinocytes to produce psoriasis-associated molecules, eventually leading to chronic skin inflammation. The current opinion is that IL-17 is mainly produced by T cells, so-called T-helper 17 (Th17) cells, in psoriasis. However, evidence is accumulating that cells of the innate immune system, like neutrophils, mast cells, cd T cells and innate lymphoid cells are the main source of IL-17 in psoriasis, rather than T cells. The paradigm in this field of research is shifting. With this viewpoint article, we will address this novel concept by critically summarizing the current literature on this subject. In psoriatic arthritis and atherosclerosis, important conditions related to psoriasis, it was also found that the majority of IL-17 is associated with cells of the innate immune system. This new concept changes our view of IL-17. Blocking IL-17 with targeted treatments might be more far-reaching than previously thought; not only IL-17 production by T cells but also by innate immune cells is blocked. Furthermore, therapies specifically targeting IL-17 may not only improve psoriasis, but also comorbidity that is associated with the IL-17 pathway, hereby preventing serious complications on the long term.

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

“…Although it has been thought that psoriasis is caused by an autoimmune mechanism,91 recent studies using mouse models suggest the involvement of innate immunity 92. High frequency of γδ T cells is detected in psoriasiform dermal lesions in mice induced by IMQ, and these cells produce IL‐17 through stimulation with IL‐23,23 indicating the innate immune nature of the disease.…”

Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

“…First, Th17 cells are not the only immune cell lineage that expresses IL-17A; other lymphocytes (γΔ + T cells) and lymphoid-like cells (type 3 innate lymphoid cells [ILC3]) are present at mucosal barriers ( e.g. , gut, lung, skin), and express IL-17A, IL-17F, and IL-22 in response to innate cytokines, such as IL-1β and IL-23 94,95 . Thus, differential accumulation and function of Th17 cells, γΔ + T cells, and ILC3s in the gut vs. skin needs to be considered and better understood.…”

Desired response to phototherapy vs photoaggravation in psoriasis: what makes the difference?

“…Importantly, IL‐17 is now recognized as a key cytokine driving the pathophysiology of psoriasis. In addition to T‐helper 17 (Th17) cells, IL‐17 can also originate from cells of the innate immune system: neutrophils, mast cells, gamma‐delta T cells and innate lymphoid cells …”