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Targeting IL-6 trans-signalling: past, present and future prospects.
Rose-John, Stefan; Jenkins, Brendan J; Garbers, Christoph; Moll, Jens M; Scheller, Jürgen.
Afiliación
  • Rose-John S; Biochemical Institute, Medical Faculty, Christian-Albrechts-University, Kiel, Germany.
  • Jenkins BJ; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
  • Garbers C; Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
  • Moll JM; Department of Pathology, Otto-von-Guericke-University Magdeburg, Medical Faculty, Magdeburg, Germany.
  • Scheller J; Health Campus Immunology, Infectiology and Inflammation (GC:I3), Otto-von-Guericke-University, Magdeburg, Germany.
Nat Rev Immunol ; 23(10): 666-681, 2023 10.
Article en En | MEDLINE | ID: mdl-37069261
Interleukin-6 (IL-6) is a key immunomodulatory cytokine that affects the pathogenesis of diverse diseases, including autoimmune diseases, chronic inflammatory conditions and cancer. Classical IL-6 signalling involves the binding of IL-6 to the membrane-bound IL-6 receptor α-subunit (hereafter termed 'mIL-6R') and glycoprotein 130 (gp130) signal-transducing subunit. By contrast, in IL-6 trans-signalling, complexes of IL-6 and the soluble form of IL-6 receptor (sIL-6R) signal via membrane-bound gp130. A third mode of IL-6 signalling - known as cluster signalling - involves preformed complexes of membrane-bound IL-6-mIL-6R on one cell activating gp130 subunits on target cells. Antibodies and small molecules have been developed that block all three forms of IL-6 signalling, but in the past decade, IL-6 trans-signalling has emerged as the predominant pathway by which IL-6 promotes disease pathogenesis. The first selective inhibitor of IL-6 trans-signalling, sgp130, has shown therapeutic potential in various preclinical models of disease and olamkicept, a sgp130Fc variant, had promising results in phase II clinical studies for inflammatory bowel disease. Technological developments have already led to next-generation sgp130 variants with increased affinity and selectivity towards IL-6 trans-signalling, along with indirect strategies to block IL-6 trans-signalling. Here, we summarize our current understanding of the biological outcomes of IL-6-mediated signalling and the potential for targeting this pathway in the clinic.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-6 / Neoplasias Límite: Humans Idioma: En Revista: Nat Rev Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-6 / Neoplasias Límite: Humans Idioma: En Revista: Nat Rev Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido