PT  - JOURNAL ARTICLE
AU  - Shengyun Ma
AU  - Yajing Hao
AU  - Benjamin S. Cho
AU  - Nicholas Chen
AU  - Anna Zheng
AU  - Shuyang Zhang
AU  - Ge Sun
AU  - Parth R. Patel
AU  - Yuxin Li
AU  - Brian A Yee
AU  - Gene W Yeo
AU  - Bing Zhou
AU  - Xiang-Dong Fu
AU  - Wendy Jia Men Huang
TI  - ADAR2 deaminase activity promotes Th17 effector function and protects against intestine inflammation
AID  - 10.1101/2020.09.22.308221
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2020.09.22.308221
4099  - http://biorxiv.org/content/early/2022/09/23/2020.09.22.308221.short
4100  - http://biorxiv.org/content/early/2022/09/23/2020.09.22.308221.full
AB  - ADAR1 and ADAR2 catalyze adenosine-to-inosine (A-to-I) editing, the most common post-transcriptional modification in RNA. While ADAR1 is ubiquitously expressed and plays a critical role in preventing activation of the host immune system, ADAR2 exhibits tissue-specific and inducible expression patterns, and its function in the immune system is not known. Here, we identify an intragenic super-enhancer involved in the dramatic induction of ADAR2 when naïve helper T cells differentiate toward the Th17 lineage. By editing the inverted repeat sequences at the 3’ untranslated region (UTR) of Malt1, which encodes a component of the NF-κB activation complex, ADAR2 promotes MALT1 expression and Th17 effector function. Interference with the ADAR2-MALT1 pathway dampens the production of Th17 cytokines and promotes T cell-mediated colitis. This study expands our understanding of RNA editing in adaptive immunity and identifies the ADAR2-MALT1-IL-17A axis as a potential therapeutic target for inflammatory conditions in the intestine.Competing Interest StatementGW Yeo is co-founder, member of the Board of Directors, on the Science Advisory Board, equity holder, and paid consultant for Locanabio and Eclipse BioInnovations. GW Yeo is a visiting professor at the National University of Singapore. The interests of GW Yeo have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies. All other authors declare no competing financial interests.