Targeting JAK/STAT signalling in inflammatory skin diseases with small molecule inhibitors

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..

For most inflammatory skin diseases topical glucocorticosteroids and traditional oral immunosuppressive drugs remain the principle treatment choices, but this has started to change. A deeper understanding in individual disease pathogenesis, basic immune mechanisms and molecular signalling pathways, together with advances in pharmaceutical drug development, allow us to interfere more precisely with disease-related factors. Some examples of inflammation-controlling interventions include antibodies neutralizing disease-associated cytokines, and small molecules targeting intracellular pathways relevant to cytokine production or cytokine signalling. So far, this is best established for psoriasis, an inflammatory skin disease dominated by Th17 cytokines. In this review, we focus on chronic inflammatory skin diseases where cytokines using type I/II cytokine receptors play a dominant role in disease pathogenesis and where novel treatments with inhibitors of the JAK/STAT pathway are already under clinical investigation. To better understand the rationale of using JAK/STAT inhibitors in the discussed skin diseases, we give an overview of important genetic and immunological associations with the JAK/STAT pathway and summarize the stage of clinical development of small molecular inhibitors. JAK/STAT inhibitors will presumably find wide application in dermatology, since they can be applied not only systematically but also topically for the treatment of inflammatory skin diseases.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:47

Enthalten in:

European journal of immunology - 47(2017), 7 vom: 14. Juli, Seite 1096-1107

Sprache:

Englisch

Beteiligte Personen:

Welsch, Katharina [VerfasserIn]
Holstein, Julia [VerfasserIn]
Laurence, Arian [VerfasserIn]
Ghoreschi, Kamran [VerfasserIn]

Links:

Volltext

Themen:

Autoimmunity
Cytokines
EC 2.7.10.2
Immunosuppressive Agents
Inflammation
JAK/STAT
JAK inhibitors
Janus Kinases
Journal Article
Protein Kinase Inhibitors
Receptors, Cytokine
Research Support, Non-U.S. Gov't
Review
STAT Transcription Factors
Skin

Anmerkungen:

Date Completed 27.09.2017

Date Revised 08.04.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/eji.201646680

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM272366862