Journal
IMMUNITY
Volume 53, Issue 2, Pages 384-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2020.06.022
Keywords
-
Categories
Funding
- NIH/National Eye Institute (NEI) [EY000184]
- Fundamental Research Funds of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center
- Natural Science Foundation of Guangdong Province [201604020082, 2017A030313836, 2019A1515010956]
- NATIONAL EYE INSTITUTE [ZIAEY000184, ZICEY000457] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Dysregulated Th17 cell responses underlie multiple inflammatory and autoimmune diseases, including autoimmune uveitis and its animal model, EAU. However, clinical trials targeting IL-17A in uveitis were not successful. Here, we report that Th17 cells were regulated by their own signature cytokine, IL-17A. Loss of IL17A in autopathogenic Th17 cells did not reduce their pathogenicity and instead elevated their expression of the Th17 cytokines GM- CSF and IL-17F. Mechanistic in vitro studies revealed a Th17 cell-intrinsic autocrine loop triggered by binding of IL-17A to its receptor, leading to activation of the transcription factor NF-kappa B and induction of IL-24, which repressed the Th17 cytokine program. In vivo, IL-24 treatment ameliorated Th17-induced EAU, whereas silencing of IL-24 in Th17 cells enhanced disease. This regulatory pathway also operated in human Th17 cells. Thus, IL-17A limits pathogenicity of Th17 cells by inducing IL-24. These findings may explain the disappointing therapeutic effect of targeting IL-17A in uveitis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available