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 and bacterial infections. Dissecting their protective vs pathologic role will allow for better therapeutics design and pharmacological intervention.

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 tissue homeostasis and 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. It has been demonstrated that IL-17 cytokine family can play a dual role during infectious processes. These cytokines may modulate host defense against pathogens through the recruitment of inflammatory cells early soon after infection, resulting in rapid pathogen eradication. If pathogens eradications fails or when inflammation plays a major pathological role, these cytokines may fuel and exacerbate inflammatory diseases through the sustainment of immunopathological processes.

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 Microbial Infection and Diseases. 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 contribution of IL-17 cytokines in microbial infections.
• IL-17 cytokine family expression and function during microbial infection
• The differential roles of IL-17 family members in host defense and immunopathology against microbial infection
• Studies on animal models helping to clarify the role of IL-17 cytokine family during microbial infections.
• Studies on human samples help to clarify the biological source of IL-17 cytokine family during pathological processes.
• 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.

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Frontiers in Immunology

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