Epithelial cell–derived cytokines: more than just signaling the alarm
Florence Roan,1,2 Kazushige Obata-Ninomiya,1 and Steven F. Ziegler1,3
1Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
2Division of Allergy and Infectious Diseases and
3Department of Immunology, University of Washington, Seattle, Washington, USA.
Address correspondence to: Steven F. Ziegler, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, Washington 98101, USA. Phone: 206.287.5657; Email: sziegler@benaroyaresearch.org.
Find articles by Roan, F. in: JCI | PubMed | Google Scholar
1Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
2Division of Allergy and Infectious Diseases and
3Department of Immunology, University of Washington, Seattle, Washington, USA.
Address correspondence to: Steven F. Ziegler, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, Washington 98101, USA. Phone: 206.287.5657; Email: sziegler@benaroyaresearch.org.
Find articles by
Obata-Ninomiya, K.
in:
JCI
|
PubMed
|
Google Scholar
|
1Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
2Division of Allergy and Infectious Diseases and
3Department of Immunology, University of Washington, Seattle, Washington, USA.
Address correspondence to: Steven F. Ziegler, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, Washington 98101, USA. Phone: 206.287.5657; Email: sziegler@benaroyaresearch.org.
Find articles by Ziegler, S. in: JCI | PubMed | Google Scholar
First published April 1, 2019 - More info
J Clin Invest. 2019;129(4):1441–1451. https://doi.org/10.1172/JCI124606.
© 2019 American Society for Clinical Investigation
The epithelial cell–derived cytokines thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 are central regulators of type 2 immunity, which drives a broad array of allergic responses. Often characterized as “alarmins” that are released by the barrier epithelium in response to external insults, these epithelial cell–derived cytokines were initially thought to act only early in allergic inflammation. Indeed, TSLP can condition dendritic cells to initiate type 2 responses, and IL-33 may influence susceptibility to asthma through its role in establishing the immune environment in the perinatal lungs. However, TSLP, IL-33, and IL-25 all regulate a broad spectrum of innate immune cell populations and are particularly potent in eliciting and activating type 2 innate lymphoid cells (ILC2s) that may act throughout allergic inflammation. Recent data suggest that a TSLP/ILC axis may mediate steroid resistance in asthma. Recent identification of memory Th2 cell subsets that are characterized by high receptor expression for TSLP, IL-33, and IL-25 further supports a role for these cytokines in allergic exacerbations. There is therefore growing interest in developing biologics that target TSLP, IL-33, and IL-25. This Review provides an overview of TSLP, IL-33, and IL-25 and the development of blocking antibodies that target these epithelial cell–derived cytokines.
- Purchase this article
- $10
- Purchasing this article will give you full access for the calendar year.
- Purchase Site Pass
- $25
- This will give you access to every article on the site for 24 hours.
- Online subscription
- $95
- Individual online subscriptions give you full online access for the calendar year.
- Individual online subscriptions ordered from September 1st on will receive access for the remainder of current year as well as for the full following year subscription term.
- Print subscription
- $830
- Individual print subscriptions give you the print journal and full online access for the year.
- JCI This Month subscription
- $125
- JCI This Month is a 16- to 20-page overview of the articles published each month
- Subscribing to JCI This Month also gives subscribers full online access for the calendar year.
- *Price outside U.S. and Canada: $225.
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)