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The JAK-STAT Signaling Pathway

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...

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Related Experiment Video

Updated: Dec 23, 2025

Expression of Exogenous Cytokine in Patient-derived Xenografts via Injection with a Cytokine-transduced Stromal Cell Line

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Published on: May 10, 2017

Translating IL-6 biology into effective treatments.

Ernest H Choy¹, Fabrizio De Benedetti², Tsutomu Takeuchi³

¹Division of Infection and Immunity, CREATE Centre, Cardiff University, Cardiff, UK. ChoyEH@Cardiff.ac.uk.

Nature Reviews. Rheumatology

|April 25, 2020

Summary

Interleukin-6 (IL-6) is crucial for immune responses and linked to numerous diseases. Therapies targeting the IL-6 pathway have shown success in treating various inflammatory and rheumatic conditions.

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Published on: June 28, 2021

Area of Science:

Immunology
Rheumatology
Molecular Biology

Background:

Interleukin-6 (IL-6), discovered in 1973, is a key cytokine involved in immune regulation.
Dysregulation of the IL-6 pathway is implicated in various autoimmune and inflammatory diseases.
The IL-6 pathway plays a critical role in both immune homeostasis and disease pathogenesis.

Purpose of the Study:

To review the history of IL-6 biology research.
To discuss the development and therapeutic applications of IL-6 pathway inhibitors.
To highlight successes and challenges in targeting IL-6 signaling, particularly in rheumatic diseases.

Main Methods:

Literature review of IL-6 research and therapeutic development.
Analysis of clinical outcomes for IL-6 targeted therapies.
Discussion of current and potential future indications for IL-6 pathway inhibition.

Main Results:

Targeting the IL-6 pathway has yielded effective therapies for rheumatoid arthritis, juvenile idiopathic arthritis, and other rheumatic conditions.
IL-6 inhibition has shown promise in treating Castleman disease, cytokine release syndrome, and is being explored for COVID-19 pneumonia.
Anti-IL-6 receptor therapy has been established for a decade, demonstrating significant clinical benefits.

Conclusions:

The IL-6 pathway is a validated target for treating a range of inflammatory and autoimmune diseases.
Continued research into IL-6 biology may uncover new therapeutic strategies and expand existing treatment indications.
Targeted IL-6 therapies represent a significant advancement in managing complex immune-mediated conditions, especially rheumatic diseases.