The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bac...

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Detalles Bibliográficos
Autores: Navarro-Compán, Victoria, Puig, Lulis, Vidal, Silvia, Ramírez, Julio, Llamas-Velasco, Mar, Fernández-Carballido, Cristina, Almodóvar, Raquel, Pinto, José Antonio, Galínez-Aguirregoikoa, Eva, Zarco, Pedro, Joven, Beatriz, Gratacós, Jordi, Juanola, Xavier, Blanco Alonso, Ricardo|||0000-0003-2344-2285, Arias-Santiago, Salvador, Sanz Sanz, Jesús, Queiro, Rubén, Cañete, Juand D.
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/30615
Acceso en línea:https://hdl.handle.net/10902/30615
Access Level:acceso abierto
Palabra clave:IL-17A
IL-17F
IL-23
Spondyloarthritis
Th17 cells
MAIT cells
gd T cells
Psoriasis
Descripción
Sumario:Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-kB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (gd) T cells, alpha beta (ab) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innatelike lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow nonredundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

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