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Understanding the IL-23-IL-17 immune pathway
Brent S McKenzie1, Robert A Kastelein, Daniel J Cua
1Discovery Research, DNAX Research Inc., 901 California Ave, Palo Alto, CA 94304-1104, USA.
Trends in Immunology
|November 18, 2005
Summary
Interleukin-23 (IL-23) drives autoimmune diseases by promoting IL-17-producing T cells and chronic inflammation. Understanding the IL-23-IL-17 pathway is crucial for distinguishing its roles in immunity versus autoimmunity.
Area of Science:
- Immunology
- Cytokine Biology
- Autoimmunity Research
Background:
- Interleukin-23 (IL-23) shares structural similarities with IL-12, including a p40 subunit.
- Despite structural resemblance, IL-23 and IL-12 exhibit distinct functional roles in immune responses.
- IL-23 is implicated in the pathogenesis of autoimmune conditions like experimental allergic encephalomyelitis, collagen-induced arthritis, and inflammatory bowel disease.
Purpose of the Study:
- To compare the pathophysiological functions of IL-12 and IL-23.
- To elucidate the role of IL-23 in host defense and autoimmune inflammation.
- To understand the novel IL-23-IL-17 immune pathway.
Main Methods:
- Comparative analysis of IL-12 and IL-23 functions.
- Investigation of immune cell involvement (T cells, neutrophils, monocytes).
- Assessment of cytokine profiles (IL-17, IL-6, IL-8, TNF).
Main Results:
- IL-23 promotes the development of autoreactive IL-17-producing T cells.
- IL-23 drives chronic inflammation characterized by specific cytokines and immune cells.
- Distinct roles of IL-23 and IL-12 in immune regulation are highlighted.
Conclusions:
- IL-23 plays a critical role in autoimmune destruction.
- The precise host benefits and evolutionary lineage of IL-17-producing cells remain to be fully clarified.
- The IL-23-IL-17 axis represents a significant pathway in immune regulation and disease.