Signal Transducer and Activator of Transcription (STAT)3 has recently emerged as a key player in the development and pathogenesis of psoriasis and psoriatic-like inflammatory conditions. Indeed, STAT3 hyperactivation has been reported in virtually every cell type involved in disease initiation and maintenance, and this factor mediates the signal of most cytokines that are involved in disease pathogenesis, including the central Interleukin (IL)-23/IL-17/IL-22 axis. Despite the recent availability of effective biological agents (monoclonal antibodies) against IL-17 and IL-23, which have radically changed the current standard of disease management, the possibility of targeting either STAT3 itself or, even better, the family of upstream activators Janus kinases (JAK1, 2, 3, and TYK2) offers additional therapeutic options. Due to the oral/topical administration modality of these small molecule drugs, their lower cost, and the reduced risk of eliciting adverse immune responses, these compounds are being actively scrutinized in clinical settings. Here, we summarize the main pathological features of psoriatic conditions that provide the rationale for targeting the JAK/STAT3 axis in disease treatment.

Psoriasis: A STAT3-centric view

Calautti, Enzo
First
;
Avalle, Lidia;Poli, Valeria
Last
2018

Abstract

Signal Transducer and Activator of Transcription (STAT)3 has recently emerged as a key player in the development and pathogenesis of psoriasis and psoriatic-like inflammatory conditions. Indeed, STAT3 hyperactivation has been reported in virtually every cell type involved in disease initiation and maintenance, and this factor mediates the signal of most cytokines that are involved in disease pathogenesis, including the central Interleukin (IL)-23/IL-17/IL-22 axis. Despite the recent availability of effective biological agents (monoclonal antibodies) against IL-17 and IL-23, which have radically changed the current standard of disease management, the possibility of targeting either STAT3 itself or, even better, the family of upstream activators Janus kinases (JAK1, 2, 3, and TYK2) offers additional therapeutic options. Due to the oral/topical administration modality of these small molecule drugs, their lower cost, and the reduced risk of eliciting adverse immune responses, these compounds are being actively scrutinized in clinical settings. Here, we summarize the main pathological features of psoriatic conditions that provide the rationale for targeting the JAK/STAT3 axis in disease treatment.
19
1
171
184
http://www.mdpi.com/1422-0067/19/1/171/pdf
psoriasis; STAT3; Th17 cells; skin inflammation; Janus kinases; autoimmunity.
Calautti, Enzo; Avalle, Lidia; Poli, Valeria*
File in questo prodotto:
File Dimensione Formato  
Calautti-Avalle-Poli-ijms-19-00171.pdf

Accesso aperto

Descrizione: Articolo principale
Tipo di file: PDF EDITORIALE
Dimensione 2.59 MB
Formato Adobe PDF
2.59 MB Adobe PDF Visualizza/Apri
Psoriasis- A STAT3-centric view.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 2.59 MB
Formato Adobe PDF
2.59 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1690830
Citazioni
  • ???jsp.display-item.citation.pmc??? 46
  • Scopus 101
  • ???jsp.display-item.citation.isi??? 91
social impact