Research Topic

The IL-17 Cytokine Family in Tissue Homeostasis and Disease

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The IL-17 cytokine family represents a wide class of pleiotropic inflammatory molecules that are structurally related. Historically the most well-known cytokines across the IL-17 family are the IL-17A, IL-17F and IL-17E (also known as IL-25) while others such as IL-17B, IL-17C or IL-17D are emerging in ...

The IL-17 cytokine family represents a wide class of pleiotropic inflammatory molecules that are structurally related. Historically the most well-known cytokines across the IL-17 family are the IL-17A, IL-17F and IL-17E (also known as IL-25) while others such as IL-17B, IL-17C or IL-17D are emerging in modulating tissue homeostasis and disease. This cytokine family activates downstream signaling through the IL-17 receptor (IL-17R) family, which includes five members named IL-17receptor(R)A, IL-17RB, IL-17RC, IL-17RE and IL-17RD. In this context, IL-17RA can play a pleiotropic role by interacting with other IL17 receptors, including IL-17RC, IL-17RB, IL-17RE and IL-17RD. Increasing evidence indicates that the IL-17 cytokines family and their receptors have a dual key role. On one hand, they play a role in tissue homeostasis and mucosal defense, while on the other hand, they play a role in different diseases including autoimmunity, chronic immune-mediated diseases and tumor immunology.

The IL-17 cytokines and receptors are expressed by a wide range of stromal and immune cells including epithelia, endothelia, fibroblasts, macrophages, neutrophils, T-helper 2 and 17, CD8+ T, T regulatory, natural killer (NK) and group 2 and 3 innate lymphoid cells.

IL-17A and IL-17F are mainly associated to type-17 response and act as pro-inflammatory molecules in several compartments such as in the gut, central nervous system, lung or skin. Both IL-17A and IL-17F cytokines can mediate pathways activated through IL-17RA/IL-17RC heterodimers. Recently, it has been proposed that IL-17A can modulate inflammation through the IL-17RA/IL-17RD receptor complex. IL-17E (IL-25) and IL-17B are known to mediate signaling related to type 2 immunity and the IL-17RA/IL-17RB heterodimers are required for down-stream signaling activation. In addition, IL17C is often associated with the mucosal host defense and is recognized by IL17RE that synergistically acts as a heterodimer with the IL-17RA.

Overall, the IL-17 cytokine family displays organ-specific inflammatory responses in several pathophysiological conditions: in the gut, skin, pancreas, spleen, liver, nervous and respiratory system as well as in cancer development. In this context, the IL-17 cytokines can modulate complex dynamic interactions between stromal and immune cells and determine the outcome of pathophysiological processes. Therefore, further efforts in the field of immunity, host-pathogen interactions and tumor immunology are required to shed light on the multifaceted IL-17 cytokines role.

In this Research Topic, we invite scientists to contribute with Reviews, Mini-Reviews and Original Research articles that will help the field to a better comprehension of the biological mechanisms mediated by the IL-17 cytokine family in health and disease. We welcome manuscripts focusing on, but not limited to, the following topics:

● Molecular and cellular mechanisms of IL-17 cytokines in health and disease.

● The emerging contribution of IL-17 cytokines in pathophysiological conditions such as autoimmunity, chronic immune-mediated diseases, and tumor immunology.

● Development of diagnostics, vaccines, and treatments targeting pathways mediated by IL-17 family members, including basic and translational research studies related to innovative pharmacological approaches.


Keywords: IL-17 cytokine family, IL-17 driven disease, IL-17 signal transduction, IL-17 therapeutics


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